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https://www.readbyqxmd.com/read/29667769/targeting-the-phosphatidylinositol-3-kinase-akt-mechanistic-target-of-rapamycin-signaling-pathway-in-b-lineage-acute-lymphoblastic-leukemia-an-update
#1
REVIEW
Carolina Simioni, Alberto M Martelli, Giorgio Zauli, Marco Vitale, James A McCubrey, Silvano Capitani, Luca M Neri
Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15-20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease...
April 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29666753/effect-of-metformin-monotherapy-on-serum-lipid-profile-in-statin-na%C3%A3-ve-individuals-with-newly-diagnosed-type-2-diabetes-mellitus-a-cohort-study
#2
Szu Han Lin, Po Chung Cheng, Shih Te Tu, Shang Ren Hsu, Yun Chung Cheng, Yu Hsiu Liu
Background: Cardiovascular disease is a major cause of mortality and morbidity in people with type 2 diabetes mellitus (T2DM). Studies have consistently identified dyslipidemia as an important risk factor for the development of macrovascular disease. The landmark United Kingdom Prospective Diabetes Study has shown that metformin therapy reduces cardiovascular events in overweight people with T2DM. This study investigates the effect of metformin monotherapy on serum lipid profile in statin-naïve individuals with newly diagnosed T2DM, and whether the effect, if any, is dosage-related...
2018: PeerJ
https://www.readbyqxmd.com/read/29666355/therapeutic-avenues-for-hereditary-forms-of-retinal-blindness
#3
Chitra Kannabiran, Indumathi Mariappan
Hereditary retinal diseases, known as retinal degenerations or dystrophies, are a large group of inherited eye disorders resulting in irreversible visual loss and blindness. They develop due to mutations in one or more genes that lead to the death of the retinal photoreceptor cells. Till date, mutations in over 200 genes are known to be associated with all different forms of retinal disorders. The enormous genetic heterogeneity of this group of diseases has posedmany challenges in understanding the mechanisms of disease and in developing suitable therapies...
March 2018: Journal of Genetics
https://www.readbyqxmd.com/read/29666288/microbiota-and-metatranscriptome-changes-accompanying-the-onset-of-gingivitis
#4
Emily M Nowicki, Raghav Shroff, Jacqueline A Singleton, Diane E Renaud, Debra Wallace, Julie Drury, Jolene Zirnheld, Brock Colleti, Andrew D Ellington, Richard J Lamont, David A Scott, Marvin Whiteley
Over half of adults experience gingivitis, a mild yet treatable form of periodontal disease caused by the overgrowth of oral microbes. Left untreated, gingivitis can progress to a more severe and irreversible disease, most commonly chronic periodontitis. While periodontal diseases are associated with a shift in the oral microbiota composition, it remains unclear how this shift impacts microbiota function early in disease progression. Here, we analyzed the transition from health to gingivitis through both 16S v4-v5 rRNA amplicon and metatranscriptome sequencing of subgingival plaque samples from individuals undergoing an experimental gingivitis treatment...
April 17, 2018: MBio
https://www.readbyqxmd.com/read/29666192/arrest-of-trans-snare-zippering-uncovers-loosely-and-tightly-docked-intermediates-in-membrane-fusion
#5
Halenur Yavuz, Iman Kattan, Javier Matias Hernandez, Oliver Hofnagel, Agata Witkowska, Stefan Raunser, Peter Jomo Walla, Reinhard Jahn
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins mediate intracellular membrane fusion in the secretory pathway. They contain conserved regions, termed SNARE motifs, that assemble between opposing membranes directionally from their N-termini to their membrane-proximal C-termini in a highly exergonic reaction. However, how this energy is utilized to overcome the energy barriers along the fusion pathway is still under debate. Here we have used mutants of the SNARE synaptobrevin to arrest trans-SNARE zippering at defined stages...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29665296/artery-first-approach-for-pancreaticoduodenectomy
#6
EDITORIAL
Manabu Kawai, Satoshi Hirano, Hiroki Yamaue
"Artery-first approach" for pancreaticoduodenectomy (PD) has gained recognition and has spread worldwide since Weitz et al. first used the term in 2010.1 , Division of the pancreatic head from the superior mesenteric artery (SMA) is traditionally performed during the final step of PD. Artery-first approach, however, has both oncological impact and better surgical technique; resectability can be determined early before committing an irreversible step during PD and blood loss may be reduced by early closure of blood flow into the pancreatic head...
April 17, 2018: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/29664627/n-%C3%AE%C2%B5-acryloyllysine-piperazides-as-irreversible-inhibitors-of-transglutaminase-2-synthesis-structure-activity-relationships-and-pharmacokinetic-profiling
#7
Robert Wodtke, Christoph Hauser, Gloria Ruiz-Gomez, Elisabeth Jäckel, David Bauer, Martin Lohse, Alan Wong, Johanna Pufe, Friedrich-Alexander Ludwig, Steffen Fischer, Sandra Hauser, Dieter Greif, Maria Teresa Pisabarro, Jens Pietzsch, Markus Pietsch, Reik Löser
Transglutaminase 2 (TGase 2)-catalysed transamidation represents an important posttranslational mechanism for protein modification with implications in physiological and pathophysiological conditions including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis and therapy of these diseases. In this study, we report on the synthesis and kinetic characterisation of Nε -acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography...
April 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29664516/-brain-development-in-childhood-acquisition-and-evolution-of-children-s-understanding-of-death
#8
Colomba Norero V
There is a relation between brain development in children and the acquisition of the five subcom ponents for a mature conceptualisation of biological death: Irreversibility, applicability, inevitability, functional cessation and casuality. Current theories propose that knowledge (among them about death) is acquired through a series of confluent waves with advances and setbacks, thus explaining the important differences encountered among children of the same age and good intellectual develop ment. Generally speaking children under four years of age do not have a consciousness of death...
February 2018: Revista Chilena de Pediatría
https://www.readbyqxmd.com/read/29664488/anodic-electrochemistry-of-mono-and-dinuclear-aminophenylferrocene-and-diphenylaminoferrocene-complexes
#9
Ming-Xing Zhang, Jing Zhang, Jun Yin, František Hartl, Sheng Hua Liu
Two related three-membered series of nonlinear aminophenylferrocene and diphenylaminoferrocene complexes were prepared and characterized by 1H and 13C NMR spectroscopy. The first series consists of 4-(diphenylamino)phenylferrocene (TPA-Fc, 1a), its dimethoxy-substituted tetraphenylphenylenediamine derivative (M2TPPD-Fc, 1c), and the triphenylamine-bridged bis(ferrocenyl) complex (Fc-TPA-Fc, 1b). The second series involves bis(4-methoxyphenyl)aminoferrocene (M2DPA-Fc, 1d), 4-methoxyphenylaminoferrocene (MPA-Fc) with N-phenyl-appended terminal TPA (1e), and the corresponding bis(MPA-Fc) complex with bridging TPA (1f)...
April 17, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29664277/nerve-agents-what-they-are-how-they-work-how-to-counter-them
#10
Stefano Costanzi, John-Hanson Machado, Moriah Mitchell
Nerve agents are organophosphorus chemical warfare agents that exert their action through the irreversible inhibition of acetylcholinesterase, with a consequent overstimulation of cholinergic transmission followed by its shutdown. Beyond warfare, they have notoriously been employed in acts of terrorism as well as high profile assassinations. After a brief historical introduction on the development and deployment of nerve agents, this review provides a survey of their chemistry, the way they affect cholinergic transmission, the available treatment options, and the current directions for their improvement...
April 17, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29664097/negishi-coupling-reactions-with-11-c-ch-3-i-a-versatile-method-for-efficient-11-c-c-bond-formation
#11
Luka Rejc, Vanessa Gómez-Vallejo, Jesús Alcázar, Nerea Alonso, José Ignacio Andrés, Ana Arrieta, Fernando P Cossío, Jordi Llop
Herein, we present a fast, efficient and general one-pot method for the synthesis of 11C-labelled compounds via the Negishi cross-coupling reaction. Our approach, based on the in situ formation of [11C]CH3ZnI and subsequent reaction with aryl halides or triflates, has proven efficient to synthesize [11C]thymidine, a biologically relevant compound with potential applications as a proliferation marker. Theoretical calculations have shown irreversible formation of a tetracoordinated nucleophilic 11C-Zn(ii) reagent and electronic requirements for an efficient Negishi coupling...
April 17, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29663674/gaba-is-an-inhibitory-neurotransmitter-in-the-neural-circuit-regulating-metamorphosis-in-a-marine-snail
#12
Dhani Biscocho, Jayce G Cook, Joshua Long, Nishant Shah, Esther M Leise
The marine mud snail, Tritia (=Ilyanassa) obsoleta, displays a biphasic life cycle. During the initial phase of early development, embryos hatch from benthic egg capsules to become weakly swimming veliger larvae. In the second phase, adult T. obsoleta are facultative carnivores and major agents of community disturbance. Metamorphosis is the irreversible developmental event that links these two life history stages. When physiologically competent, larvae can respond to appropriate environmental cues by settling onto their mudflat habitat and transforming themselves into miniature adult snails...
April 16, 2018: Developmental Neurobiology
https://www.readbyqxmd.com/read/29663317/atrophic-scar-formation-in-acne-patients-involves-long-acting-immune-responses-with-plasma-cells-and-alteration-of-sebaceous-glands
#13
I Carlavan, B Bertino, M Rivier, P Martel, V Bourdes, M Motte, S Déret, P Reiniche, C Menigot, A Khammari, B Dreno, P Fogel, J J Voegel
BACKGROUND: Possible outcomes of acne lesions are atrophic scars which may cause serious psychological distress. Current treatments of post-acne scarring often require invasive procedures. Pathophysiological studies on acne scarring investigated only the first week of papule life. OBJECTIVES: Study the pathophysiology of atrophic scar formation to identify molecular and cellular pathways that can lead to new therapies for the prevention of acne scarring. METHODS: Large-scale gene expression profiling and immunohistochemistry analysis were performed on uninvolved skin and papules in both, scar-prone (SP) and non-scar-prone (NSP) acne patients, at different time points...
April 16, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29663261/evaluation-of-diffusion-tensor-imaging-changes-and-neurocognitive-effects-of-asymptomatic-vitamin-b12-deficiency
#14
Ali Zeynal Abidin Tak, Erdal Dayan, Hacı Taner Bulut
Vitamin B12 plays an important role in the mechanisms which are responsible for myelinization in the central nervous system. It can particularly lead to hematological and neuropsychiatric symptoms when serum levels fall due to insufficient intake with diet or absorption problems. The purpose of this study was to show the cognitive effects in vitamin B12 deficiency cases that have not reached clinical symptom level using neuropsychological tests, and to show possible cerebral neuronal damage using diffusion tensor imaging (DTI) method...
April 16, 2018: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/29662989/group-3-metal-trihalide-complexes-with-neutral-n-donor-ligands-exploring-their-affinity-towards-fluoride
#15
Emily Curnock, William Levason, Mark E Light, Sajinder K Luthra, Graeme McRobbie, Francesco M Monzittu, Gillian Reid, R Nathan Williams
Fluorination of [ScCl3(Me3-tacn)] (Me3-tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane) and [ScCl3(BnMe2-tacn)] (BnMe2-tacn = 1,4-dimethyl-7-benzyl-1,4,7-triazacyclononane) by Cl/F exchange with 3 mol. equiv. of anhydrous [NMe4]F in CH3CN solution yields the corresponding [ScF3(R3-tacn)] (R3 = Me3 or BnMe2). These are the first examples of scandium fluoride complexes containing neutral co-ligands. The fluorination occurs stepwise, and using a deficit of [NMe4]F produced [ScF2Cl(Me3-tacn)]. Attempts to fluorinate [YCl3(Me3-tacn)], [YI3(Me3-tacn)], [LaCl3(Me3-tacn)(OH2)] or [MCl3(terpy)] (M = Sc, Y or La; terpy = 2,2':6'2''-terpyridyl) using a similar method were unsuccessful, due to the Cl/F exchange being accompanied by loss of the neutral ligand from the metal centre...
April 17, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29662476/improvement-of-the-uranium-sequestration-ability-of-a-chlamydomonas-sp-chlsp-strain-isolated-from-extreme-uranium-mine-tailings-through-selection-for-potential-bioremediation-application
#16
Beatriz Baselga-Cervera, Julia Romero-López, Camino García-Balboa, Eduardo Costas, Victoria López-Rodas
The extraction and processing of uranium (U) have polluted large areas worldwide, rendering anthropogenic extreme environments inhospitable to most species. Noticeably, these sites are of great interest for taxonomical and applied bioprospection of extremotolerant species successfully adapted to U tailings contamination. As an example, in this work we have studied a microalgae species that inhabits extreme U tailings ponds at the Saelices mining site (Salamanca, Spain), characterized as acidic (pH between 3 and 4), radioactive (around 4 μSv h-1 ) and contaminated with metals, mainly U (from 25 to 48 mg L-1 ) and zinc (from 17 to 87 mg L-1 )...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29662200/targeting-sphingosine-1-phosphate-lyase-as-an-anabolic-therapy-for-bone-loss
#17
Sarah Weske, Mithila Vaidya, Alina Reese, Karin von Wnuck Lipinski, Petra Keul, Julia K Bayer, Jens W Fischer, Ulrich Flögel, Jens Nelsen, Matthias Epple, Marta Scatena, Edzard Schwedhelm, Marcus Dörr, Henry Völzke, Eileen Moritz, Anke Hannemann, Bernhard H Rauch, Markus H Gräler, Gerd Heusch, Bodo Levkau
Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its therapeutic potential in bone disorders has remained unexplored. We show that raising S1P levels in adult mice through conditionally deleting or pharmacologically inhibiting S1P lyase, the sole enzyme responsible for irreversibly degrading S1P, markedly increased bone formation, mass and strength and substantially decreased white adipose tissue. S1P signaling through S1P2 potently stimulated osteoblastogenesis at the expense of adipogenesis by inversely regulating osterix and PPAR-γ, and it simultaneously inhibited osteoclastogenesis by inducing osteoprotegerin through newly discovered p38-GSK3β-β-catenin and WNT5A-LRP5 pathways...
April 16, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29662160/highly-reversible-zinc-metal-anode-for-aqueous-batteries
#18
Fei Wang, Oleg Borodin, Tao Gao, Xiulin Fan, Wei Sun, Fudong Han, Antonio Faraone, Joseph A Dura, Kang Xu, Chunsheng Wang
Metallic zinc (Zn) has been regarded as an ideal anode material for aqueous batteries because of its high theoretical capacity (820 mA h g-1 ), low potential (-0.762 V versus the standard hydrogen electrode), high abundance, low toxicity and intrinsic safety. However, aqueous Zn chemistry persistently suffers from irreversibility issues, as exemplified by its low coulombic efficiency (CE) and dendrite growth during plating/ stripping, and sustained water consumption. In this work, we demonstrate that an aqueous electrolyte based on Zn and lithium salts at high concentrations is a very effective way to address these issues...
April 16, 2018: Nature Materials
https://www.readbyqxmd.com/read/29661566/lichen-planopilaris-and-frontal-fibrosing-alopecia-as-model-epithelial-stem-cell-diseases
#19
REVIEW
Matthew J Harries, Francisco Jimenez, Ander Izeta, Jonathan Hardman, Sreejith Parameswara Panicker, Enrique Poblet, Ralf Paus
Inflammation-associated, irreversible damage to epithelial stem cells (eSCs) of the hair follicle in their immunologically privileged niche lies at the heart of scarring alopecia, which causes permanent difficult-to-treat hair loss. We propose that the two most common and closely related forms, lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA), provide excellent model diseases for studying the biology and pathology of adult human eSCs in an easily accessible human mini-organ. Emphasising the critical roles for interferon (IFN)-γ and peroxisome proliferator-activated receptor (PPAR)-γ-mediated signalling in immune privilege (IP) collapse and epithelial-mesenchymal transition (EMT) of these eSCs respectively, we argue that these pathways deserve therapeutic targeting in the future management of LPP/FFA and other eSC diseases associated with IP collapse and EMT...
April 13, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29661461/urgent-living-donor-liver-transplantation-in-a-patient-with-concurrent-active-tuberculosis-a-case-report
#20
B-H Jung, J-I Park, S-G Lee
BACKGROUND: Although active tuberculosis (TB) is considered a contraindication for liver transplantation (LT), this is the only treatment in patients with liver failure and concurrent active TB. We report a case with successful urgent living-donor LT for irreversible liver failure in the presence of active TB. CASE PRESENTATION: A 48-year-old man, with a history of decompensated alcoholic liver cirrhosis, was presented with stupor. At admission, his consciousness had deteriorated to semi-coma, and his renal function also rapidly deteriorated to hepatorenal syndrome...
April 2018: Transplantation Proceedings
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