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Slow Pathway Modification

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...
October 13, 2016: 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 3, 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
Teodor Adrian Enache, Ana-Maria Chiorcea-Paquim, Ana Maria Oliveira-Brett
The human amyloid beta (Aβ) peptides, Aβ1-40 and Aβ1-42, structural modifications, from soluble monomers to fully formed fibrils through intermediate structures, were investigated, and the results were compared with those obtained for the inverse Aβ40-1 and Aβ42-1, mutant Aβ1-40Phe(10) and Aβ1-40Nle(35), and rat Aβ1-40Rat peptide sequences. The aggregation was followed at a slow rate, in chloride free media and room temperature, and revealed to be a sequence-structure process, dependent on the physicochemical properties of each Aβ peptide isoforms, and occurring at different rates and by different pathways...
July 5, 2016: Analytica Chimica Acta
Xun Sun, James H Park, Jessica Gumerson, Zhijian Wu, Anand Swaroop, Haohua Qian, Antonina Roll-Mecak, Tiansen Li
Mutations in the X-linked retinitis pigmentosa GTPase regulator (RPGR) gene are a major cause of retinitis pigmentosa, a blinding retinal disease resulting from photoreceptor degeneration. A photoreceptor specific ORF15 variant of RPGR (RPGR(ORF15)), carrying multiple Glu-Gly tandem repeats and a C-terminal basic domain of unknown function, localizes to the connecting cilium where it is thought to regulate cargo trafficking. Here we show that tubulin tyrosine ligase like-5 (TTLL5) glutamylates RPGR(ORF15) in its Glu-Gly-rich repetitive region containing motifs homologous to the α-tubulin C-terminal tail...
May 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
Felix K Wegner, Maria Silvano, Nils Bögeholz, Patrick R Leitz, Gerrit Frommeyer, Dirk G Dechering, Stephan Zellerhoff, Simon Kochhäuser, Philipp S Lange, Julia Köbe, Kristina Wasmer, Gerold Mönnig, Lars Eckardt, Christian Pott
BACKGROUND: Slow pathway modification (SPM) is the therapy of choice for AV-nodal reentry tachycardia (AVNRT). When AVNRT is not inducible, empirical ablation can be considered, however, the outcome in patients with two AV nodal echo beats (AVNEBs) is unknown. METHODS: Out of a population of 3003 patients who underwent slow pathway modification at our institution between 1993 and 2013, we retrospectively included 32 patients with a history of symptomatic tachycardia, lack of paroxysmal supraventricular tachycardia (pSVT) inducibility but occurrence of two AVNEBs...
March 25, 2016: Journal of Cardiology
Lea Schaaf, Matthias Schwab, Christoph Ulmer, Simon Heine, Thomas E Mürdter, Jens O Schmid, Georg Sauer, Walter E Aulitzky, Heiko van der Kuip
Although hyperthermia offers clinical appeal to sensitize cells to chemotherapy, this approach has been limited in terms of long-term outcome as well as economic and technical burden. Thus, a more detailed knowledge about how hyperthermia exerts its effects on chemotherapy may illuminate ways to improve the approach. Here, we asked whether hyperthermia alters the response to chemotherapy-induced DNA damage and whether this mechanism is involved in its sensitizing effect in BRCA-competent models of ovarian and colon cancer...
May 15, 2016: Cancer Research
Sonja M Wörmann, Liang Song, Jiaoyu Ai, Kalliope N Diakopoulos, Magdalena U Kurkowski, Kivanc Görgülü, Dietrich Ruess, Andrew Campbell, Claudio Doglioni, Duncan Jodrell, Albrecht Neesse, Ihsan E Demir, Angelica-Phaedra Karpathaki, Maxim Barenboim, Thorsten Hagemann, Stefan Rose-John, Owen Sansom, Roland M Schmid, Maria P Protti, Marina Lesina, Hana Algül
BACKGROUND & AIMS: One treatment strategy for pancreatic ductal adenocarcinoma is to modify, rather than deplete, the tumor stroma. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) is associated with progression of pancreatic and other solid tumors. We investigated whether loss of P53 function contributes to persistent activation of STAT3 and modification of the pancreatic tumor stroma in patients and mice. METHODS: Stat3, Il6st (encodes gp130), or Trp53 were disrupted, or a mutant form of P53 (P53R172H) or transgenic sgp130 were expressed, in mice that developed pancreatic tumors resulting from expression of activated KRAS (KrasG12D, KC mice)...
July 2016: Gastroenterology
Emily Sue Ruckdeschel, Joseph Kay, Paul Varosy, Duy Thai Nguyen
Patients with systemic right ventricles are often not able to tolerate frequent, rapid, or incessant atrial arrhythmias without developing significant symptoms and ventricular dysfunction. Atrial arrhythmias are associated with an increased risk of ventricular arrhythmias and sudden cardiac death. Rhythm disturbances must be aggressively addressed in this population with frequent screening, follow-up, and treatment.
March 2016: Cardiac Electrophysiology Clinics
David K Singh, Nitish Badhwar
This article reports a typical case of incessant double-fire tachycardia resulting in implantable cardioverter-defibrillator discharge caused by the device's misdiagnosis of ventricular tachycardia. At electrophysiology study, the presence of double-fire physiology was confirmed, and modification of the slow pathway resulted in elimination of repetitive double fires. Although this is an unusual entity, it is important to recognize, because it may be misdiagnosed as atrial fibrillation, resulting in inappropriate anticoagulation and/or antiarrhythmic therapy...
March 2016: Cardiac Electrophysiology Clinics
Barbara A Niemeyer
A wide variety of cellular function depends on the dynamics of intracellular Ca(2+) signals. Especially for relatively slow and lasting processes such as gene expression, cell proliferation, and often migration, cells rely on the store-operated Ca(2+) entry (SOCE) pathway, which is particularly prominent in immune cells. SOCE is initiated by the sensor proteins (STIM1, STIM2) located within the endoplasmic reticulum (ER) registering the Ca(2+) concentration within the ER, and upon its depletion, cluster and trap Orai (Orai1-3) proteins located in the plasma membrane (PM) into ER-PM junctions...
May 1, 2016: American Journal of Physiology. Cell Physiology
Tatsuo Yanagisawa, Hideyuki Takahashi, Takehiro Suzuki, Akiko Masuda, Naoshi Dohmae, Shigeyuki Yokoyama
Translation elongation factor P (EF-P), a ubiquitous protein over the entire range of bacterial species, rescues ribosomal stalling at consecutive prolines in proteins. In Escherichia coli and Salmonella enterica, the post-translational β-lysyl modification of Lys34 of EF-P is important for the EF-P activity. The β-lysyl EF-P modification pathway is conserved among only 26-28% of bacteria. Recently, it was found that the Shewanella oneidensis and Pseudomonas aeruginosa EF-P proteins, containing an Arg residue at position 32, are modified with rhamnose, which is a novel post-translational modification...
2016: PloS One
Shailendra Upadhyay, Anne Marie Valente, John K Triedman, Edward P Walsh
BACKGROUND: Variability in atrioventricular (AV) node location in congenital heart disease (CHD) can make catheter ablation for atrioventricular nodal reentrant tachycardia (AVNRT) challenging. OBJECTIVE: The purpose of this study was to describe institutional technique and outcomes for slow pathway modification in a cohort with CHD. METHODS: The study consisted of a retrospective review of CHD patients who underwent study from 2001 to 2013 with a diagnosis of AVNRT...
June 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Patrick C Thiaville, Rachel Legendre, Diego Rojas-Benítez, Agnès Baudin-Baillieu, Isabelle Hatin, Guilhem Chalancon, Alvaro Glavic, Olivier Namy, Valérie de Crécy-Lagard
The universal tRNA modification t(6)A is found at position 37 of nearly all tRNAs decoding ANN codons. The absence of t(6)A37 leads to severe growth defects in baker's yeast, phenotypes similar to those caused by defects in mcm(5)s(2)U34 synthesis. Mutants in mcm(5)s(2)U34 can be suppressed by overexpression of tRNA(Lys) UUU, but we show t(6)A phenotypes could not be suppressed by expressing any individual ANN decoding tRNA, and t(6)A and mcm(5)s(2)U are not determinants for each other's formation. Our results suggest that t(6)A deficiency, like mcm(5)s(2)U deficiency, leads to protein folding defects, and show that the absence of t(6)A led to stress sensitivities (heat, ethanol, salt) and sensitivity to TOR pathway inhibitors...
January 1, 2016: Microbial Cell
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