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Slow Pathway Modification

Hyeonju Woo, So Dam Ha, Sung Bae Lee, Stephen Buratowski, TaeSoo Kim
Co-transcriptional methylations of histone H3 at lysines 4 and 36, highly conserved methyl marks from yeast to humans, have profound roles in regulation of histone acetylation. These modifications function to recruit and/or activate distinct histone acetyltransferases (HATs) or histone deacetylases (HDACs). Whereas H3K4me3 increases acetylation at promoters via multiple HATs, H3K4me2 targets Set3 HDAC to deacetylate histones in 5' transcribed regions. In 3' regions of genes, H3K36me2/3 facilitates deacetylation by Rpd3S HDAC and slows elongation...
April 28, 2017: Experimental & Molecular Medicine
Henry Ng, Neta Dean
The clustered regularly interspaced short palindromic repeat system with CRISPR-associated protein 9 nuclease (CRISPR/Cas9) has emerged as a versatile tool for genome editing in Candida albicans. Mounting evidence from other model systems suggests that the intracellular levels of single guide RNA (sgRNA) limit the efficiency of Cas9-dependent DNA cleavage. Here, we tested this idea and describe a new means of sgRNA delivery that improves previously described methods by ~10-fold. The efficiency of Cas9/sgRNA-dependent cleavage and repair of a single-copy yeast enhanced monomeric red fluorescent protein (RFP) gene was measured as a function of various parameters that are hypothesized to affect sgRNA accumulation, including transcriptional and posttranscriptional processing...
March 2017: MSphere
Bo Bae Lee, Ji Hyun Kim, TaeSoo Kim
RNA polymerase II-interacting the Set2 methyltransferase co-transcriptionally methylates histone H3 at lysine 36 within the body of genes. This modification facilitates histone deacetylation by Rpd3S HDAC in 3' transcribed regions to suppress cryptic initiation and slow elongation. Although this pathway is important for global deacetylation, no strong effects have been seen on genome-wide transcription under optimized laboratory conditions. In contrast, this pathway slows the kinetics of mRNA induction when target genes are induced upon environmental changes...
April 2017: BMB Reports
E A Rudnitskaya, N G Kolosova, N A Stefanova
Alzheimer's disease (AD) is the most common type of age-related dementia. The development of neurodegeneration in AD is closely related to alterations in neurotrophic supplementation of the brain, which may be caused either by disorder of neurotrophin metabolism or by modification of its availability due to changes in the microenvironment of neurons. The underlying mechanisms are not fully understood. In this work, we used senescence-accelerated OXYS rats as a unique model of the sporadic form of AD to examine the relationship of development of AD signs and changes in neurotrophic supplementation of the cortex...
March 2017: Biochemistry. Biokhimii︠a︡
Abhishek Bhaskaran, Maha Albarri, Neil Ross, Sara Al Raisi, Rahul Samantha, Leonette Roode, Fazlur Nadri, Jeanette Ng, Stuart Thomas, Aravinda Thiagalingam, Pramesh Kovoor
BACKGROUND: The Magnetic Navigation System (MNS) catheter was shown to be stable in the presence of significant cardiac wall motion and delivered more effective lesions compared to manual control. This stability could potentially make AV junctional reentrant tachycardia (AVNRT) ablation safer. The aim of this study is to describe the method of mapping and ablation of AVNRT with MNS and 3-D electro-anatomical mapping system (CARTO, Biosense Webster, Diamond bar, CA, USA) anatomical mapping, with a view to improve the safety of ablation...
February 21, 2017: Heart, Lung & Circulation
Amol Sharma, Satish Rao
Chronic constipation is a common, persistent condition affecting many patients worldwide, presenting significant economic burden and resulting in substantial healthcare utilization. In addition to infrequent bowel movements, the definition of constipation includes excessive straining, a sense of incomplete evacuation, failed or lengthy attempts to defecate, use of digital manoeuvres for evacuation of stool, abdominal bloating, and hard consistency of stools. After excluding secondary causes of constipation, chronic idiopathic or primary constipation can be classified as functional defecation disorder, slow-transit constipation (STC), and constipation-predominant irritable bowel syndrome (IBS-C)...
2017: Handbook of Experimental Pharmacology
Alexandre A S Gonçalves, Patrícia B Faustino, José M Assaf, Mietek Jaroniec
One-pot synthesis of nanostructured ternary oxides of Ni, Al, and Ti was designed and performed via evaporation induced self-assembly (EISA). For the purpose of comparison, analogous oxides were also prepared by the impregnation method. The resulting materials were applied in two catalytic reactions: steam reforming of ethanol (SRE) for H2 production (subjected to prior activation with H2) and ethanol dehydration (ED; used without prior activation), to in situ analyze carbon accumulation by ethylene depletion when ethanol interacts with acidic sites present on the support...
February 22, 2017: ACS Applied Materials & Interfaces
Eli A Sutter, Peter W Sutter
Galvanic replacement reactions are important as they transform nanoparticle templates into complex porous and hollow metal or alloy nanostructures with interesting properties for a variety of applications. Real-time liquid cell electron microscopy (LCEM) observations of the transformation of solid nanoparticles into hollow shell and cage bimetallic nanostructures are challenging because the high-energy electron beam strongly affects the galvanic process via species such as aqueous electrons and hydroxyl radicals generated through the radiolysis of water in the liquid cell...
January 19, 2017: Nanoscale
Xiangyu Liu, Feifei Li, Xiaohui Ma, Peipei Cen, Shuchang Luo, Quan Shi, Shenru Ma, Yuewei Wu, Chengcheng Zhang, Zhao Xu, Weiming Song, Gang Xie, Sanping Chen
Employing two benzoate derivatives with different numbers of non-coordinated fluoro-substituents, 2-fluorobenzoic acid (2-Hfba) and 2,6-difluorobenzoic acid (2,6-Hdfba), two new azido-copper coordination polymers, [Cu(2-fba)(N3)(CH3OH)]n (1) and [Cu(2,6-dfba)(N3)(CH3OH)]n (2), have been successfully isolated, and then structurally and magnetically investigated. Single crystal structure analysis demonstrates that the metal cations in the two resulting compounds are connected by the alternating triple-bridge of μ-1,1-azido, syn,syn-carboxylate and μ2-methanol, contributing to analogously linear 1D Cu(ii) chain-like motifs with slightly different intrachain and interchain geometric parameters...
January 5, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
Juan Ignacio Ramos-Martinez
The changes in gene expression and posttranslational modifications of enzymes are comprised in the concept of "coarse control" of the oxidative phase of the pentose phosphate pathway. However, these changes are slow in its implementation. The defensive mechanism against oxidative stress requires a most rapid response, impossible to achieve with coarse regulation systems. Recently, it has been suggested that a quick acceleration mechanism of G6PD activity could be produced by the reduction of NADPH-inhibition of G6PD...
January 15, 2017: Archives of Biochemistry and Biophysics
Joseph R Peterson, ShengShee Thor, Lars Kohler, Petra R A Kohler, William W Metcalf, Zaida Luthey-Schulten
BACKGROUND: While a few studies on the variations in mRNA expression and half-lives measured under different growth conditions have been used to predict patterns of regulation in bacterial organisms, the extent to which this information can also play a role in defining metabolic phenotypes has yet to be examined systematically. Here we present the first comprehensive study for a model methanogen. RESULTS: We use expression and half-life data for the methanogen Methanosarcina acetivorans growing on fast- and slow-growth substrates to examine the regulation of its genes...
November 16, 2016: BMC Genomics
Khalid Rehman Hakeem, Muhammad Sabir, Munir Ozturk, Mohd Sayeed Akhtar, Faridah Hanum Ibrahim, Muhammad Ashraf, Muhammad Sajid Aqeel Ahmad
Increased use of nitrogenous (N) fertilizers in agriculture has significantly altered the global N-cycle because they release nitrogenous gases of environmental concerns. The emission of nitrous oxide (N2O) contributes to the global greenhouse gas accumulation and the stratospheric ozone depletion. In addition, it causes nitrate leaching problem deteriorating ground water quality. The nitrate toxicity has been reported in a number of studies showing the health hazards like methemoglobinemia in infants and is a potent cause of cancer...
2017: Reviews of Environmental Contamination and Toxicology
D Athauda, T Foltynie
There is growing evidence that patients with Type 2 diabetes have an increased risk of developing Parkinson's disease and share similar dysregulated pathways suggesting common underlying pathological mechanisms. Historically insulin was thought solely to be a peripherally acting hormone responsible for glucose homeostasis and energy metabolism. However accumulating evidence indicates insulin can cross the blood-brain-barrier and influence a multitude of processes in the brain including regulating neuronal survival and growth, dopaminergic transmission, maintenance of synapses and pathways involved in cognition...
October 2016: Progress in Neurobiology
Hayate Javed, Mohammad Amjad Kamal, Shreesh Ojha
Parkinson's disease (PD) is a devastating and progressive movement disorder characterized by symptoms of muscles rigidity, tremor, postural instability and slow physical movements. Biochemically, PD is characterized by lack of dopamine production and its action due to loss of dopaminergic neurons and neuropathologically by the presence of intracytoplasmic inclusions known as Lewy bodies, which mainly consist of presynaptic neuronal protein, α-synuclein (α-syn). It is believed that alteration in α-syn homeostasis leads to increased accumulation and aggregation of α-syn in Lewy body...
September 20, 2016: CNS & Neurological Disorders Drug Targets
Jacqueline E Reilly, Jeffrey D Neighbors, Raymond J Hohl
The isoprenoid biosynthetic pathway (IBP) plays a critical role in providing substrates and enzymes necessary for the post-translational modification and thus activation of a number of proteins involved in prostate cancer metastasis. Previous work by our lab found novel compound disodium [(6Z,11E,15E)-9-[bis(sodiooxy)phosphoryl]-17-hydroxy-2,6,12,16-tetramethyheptadeca-2,6,11,15-tetraen-9-yl]phosphonate (GGOHBP), which inhibits the IBP enzyme geranylgeranyl diphosphate synthase (GGDPS), reduced protein geranylgeranylation without altering protein farnesylation...
September 13, 2016: Cancer Biology & Therapy
Silvia Gangemi, Eliza Gofita, Chiara Costa, Michele Teodoro, Giusi Briguglio, Dragana Nikitovic, George Tzanakakis, Aristides M Tsatsakis, Martin F Wilks, Demetrios A Spandidos, Concettina Fenga
Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear...
October 2016: International Journal of Molecular Medicine
Jérome Chal, Ziad Al Tanoury, Marie Hestin, Bénédicte Gobert, Suvi Aivio, Aurore Hick, Thomas Cherrier, Alexander P Nesmith, Kevin K Parker, Olivier Pourquié
Progress toward finding a cure for muscle diseases has been slow because of the absence of relevant cellular models and the lack of a reliable source of muscle progenitors for biomedical investigation. Here we report an optimized serum-free differentiation protocol to efficiently produce striated, millimeter-long muscle fibers together with satellite-like cells from human pluripotent stem cells (hPSCs) in vitro. By mimicking key signaling events leading to muscle formation in the embryo, in particular the dual modulation of Wnt and bone morphogenetic protein (BMP) pathway signaling, this directed differentiation protocol avoids the requirement for genetic modifications or cell sorting...
October 2016: Nature Protocols
Imanol de Pedro, Oscar Fabelo, Abel García-Saiz, Oriol Vallcorba, Javier Junquera, Jesús Angel Blanco, João Carlos Waerenborgh, D Andreica, Andrew Wildes, María Teresa Fernández-Díaz, Jesús Rodríguez Fernández
The results reported here represent the first direct experimental observations supporting the existence of a solid-to-solid phase transition induced by thermal treatment in magnetic ionic liquids (MILs). The phase transitions of the solid phases of 1,3-dimethylimidazolium tetrachloroferrate, DimimFeCl4, are closely related to its thermal history. Two series of solid-to-solid phase transitions can be described in this MIL: (i) from room temperature (RT) phase II [space group (s.g.) = P21] to phase I-a [s.g. = P212121] via thermal quenching or via fast cooling at T > 2 K min(-1); (ii) from phase I-a to phase I-b [s...
August 3, 2016: Physical Chemistry Chemical Physics: PCCP
M Perluigi, E Barone, F Di Domenico, D A Butterfield
Protein phosphorylation of serine, threonine, and tyrosine residues is one of the most prevalent post-translational modifications fundamental in mediating diverse cellular functions in living cells. Aberrant protein phosphorylation is currently recognized as a critical step in the pathogenesis and progression of Alzheimer disease (AD). Changes in the pattern of protein phosphorylation of different brain regions are suggested to promote AD transition from a presymptomatic to a symptomatic state in response to accumulating amyloid β-peptide (Aβ)...
October 2016: Biochimica et Biophysica Acta
Caroline Van Cauwenberghe, Charysse Vandendriessche, Claude Libert, Roosmarijn E Vandenbroucke
Dietary interventions such as caloric restriction (CR) extend lifespan and health span. Recent data from animal and human studies indicate that CR slows down the aging process, benefits general health, and improves memory performance. Caloric restriction also retards and slows down the progression of different age-related diseases, such as Alzheimer's disease. However, the specific molecular basis of these effects remains unclear. A better understanding of the pathways underlying these effects could pave the way to novel preventive or therapeutic strategies...
August 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
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