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https://www.readbyqxmd.com/read/29457724/regio-and-stereoselective-synthesis-of-isoindolin-1-ones-through-buli-mediated-iodoaminocyclization-of-2-1-alkynyl-benzamides
#1
Dhirendra Brahmchari, Akhilesh K Verma, Saurabh Mehta
A simple and straightforward synthesis of isoindolin-1-ones is reported. Exclusive N-cyclization of the amide functional group, an ambident nucleophile, has been accomplished for the cyclization of 2-(1-alkynyl)benzamides using n-BuLi-I2 /ICl. The methodology works with the primary amide and affords the desired isoindolinones in yields of 38-94%. Interestingly, the isolated products exhibit a Z-stereochemistry across the C=C double bond. The reaction mechanism involving the formation of either a vinylic anion or an intimate ion pair intermediate is proposed...
February 19, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29423082/reduced-recruitment-of-53bp1-during-interstrand-crosslink-repair-is-associated-with-genetically-inherited-attenuation-of-mitomycin-c-sensitivity-in-a-family-with-fanconi-anemia
#2
Emilie Lesport, Alina Ferster, Armand Biver, Benoit Roch, Nadia Vasquez, Nada Jabado, Francina Langa Vives, Patrick Revy, Jean Soulier, Jean-Pierre de Villartay
The Fanconi anemia (FA) pathway is implicated in the repair of DNA interstrand crosslinks (ICL). In this process, it has been shown that FA factors regulate the choice for DNA double strand break repair towards homologous recombination (HR). As this mechanism is impaired in FA deficient cells exposed to crosslinking agents, an inappropriate usage of non-homologous end joining (NHEJ) leads to the accumulation of toxic chromosomal abnormalities. We studied a family with two FANCG patients and found a genetically inherited attenuation of mitomycin C sensitivity resulting in-vitro in an attenuated phenotype for one patient or in increased resistance for two healthy relatives...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29421809/a-potassium-selective-current-affected-by-micromolar-concentrations-of-anion-transport-inhibitors
#3
Roberta Costa, Davide Antonio Civello, Emanuele Bernardinelli, Simone Vanoni, Michaela Zopf, Giada Scantamburlo, Charity Nofziger, Wolfgang Patsch, Markus Paulmichl, Silvia Dossena
BACKGROUND/AIMS: In the human genome, more than 400 genes encode ion channels, which are ubiquitously expressed and often coexist and participate in almost all physiological processes. Therefore, ion channel blockers represent fundamental tools in discriminating the contribution of individual channel types to a physiological phenomenon. However, unspecific effects of these compounds may represent a confounding factor. Three commonly used chloride channel inhibitors, i.e. 4,4'-diisothiocyano-2,2'-stilbene-disulfonic acid (DIDS), 5-nitro-2-[(3-phenylpropyl) amino]benzoic acid (NPPB) and the anti-inflammatory drug niflumic acid were tested to identify the lowest concentration effective on Cl- channels and ineffective on K+ channels...
February 2, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29416673/splice-variants-of-the-endonucleases-xpf-and-xpg-contain-residual-dna-repair-capabilities-and-could-be-a-valuable-tool-for-personalized-medicine
#4
Janin Lehmann, Steffen Schubert, Christina Seebode, Antje Apel, Andreas Ohlenbusch, Steffen Emmert
The two endonucleases XPF and XPG are essentially involved in nucleotide excision repair (NER) and interstrand crosslink (ICL) repair. Defects in these two proteins result in severe diseases like xeroderma pigmentosum (XP). We applied our newly CRISPR/Cas9 generated human XPF knockout cell line with complete loss of XPF and primary fibroblasts from an XP-G patient (XP20BE) to analyze until now uncharacterized spontaneous mRNA splice variants of these two endonucleases. Functional analyses of these variants were performed using luciferase-based reporter gene assays...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29414879/determining-biogenic-content-of-biogas-by-measuring-stable-isotopologues-12ch%C3%A2-13ch%C3%A2-and-ch%C3%A2-d-with-a-mid-infrared-direct-absorption-laser-spectrometer
#5
Teemu Kääriäinen, Craig A Richmond, Albert Manninen
A tunable laser absorption spectrometer (TLAS) was developed for the simultaneous measurement of δ13C and δD values of methane (CH₄). A mid-infrared interband cascade laser (ICL) emitting around 3.27 µm was used to measure the absorption of the three most abundant isotopologues in CH₄ with a single, mode-hop free current sweep. The instrument was validated against methane samples of fossil and biogenic origin with known isotopic composition. Three blended mixtures with varied biogenic content were prepared volumetrically, and their δ13C and δD values were determined...
February 7, 2018: Sensors
https://www.readbyqxmd.com/read/29395689/effect-of-gnrh-analogue-administration-on-day-7-after-natural-mating-on-formation-accessory-corpus-luteum-progesterone-concentration-and-conception-rate-in-llamas-lama-glama
#6
Marcos C Abalos, Francisco Acuña, Andrea K Cancino, Juan F Aller
The objectives of the present study were to determine the effects of exogenous GnRH administered 7 days after breeding on the formation of an accessory corpus luteum (ACL), plasma progesterone (P4) concentrations and pregnancy rates. Adult females (n = 71) having a follicle ≥ 7 mm in diameter in the ovary were naturally mated (Day 0). On Day 7, ultrasonic examination was performed to confirm the occurrence of ovulation as evidenced by presence of an induced corpus luteum (ICL). Females with an ICL plus a dominant follicle ≥ 7 mm (n = 56) were treated with saline solution (SS, n = 29) or GnRH analogue (n = 27)...
January 29, 2018: Animal Reproduction Science
https://www.readbyqxmd.com/read/29385679/the-molecular-mechanisms-of-plant-derived-compounds-targeting-brain-cancer
#7
REVIEW
Hueng-Chuen Fan, Ching-Shiang Chi, Yu-Kang Chang, Min-Che Tung, Shinn-Zong Lin, Horng-Jyh Harn
Glioblastoma multiforme (GBM) is one of the most aggressive and malignant forms of brain tumors. Despite recent advances in operative and postoperative treatments, it is almost impossible to perform complete resection of these tumors owing to their invasive and diffuse nature. Several natural plant-derived products, however, have been demonstrated to have promising therapeutic effects, such that they may serve as resources for anticancer drug discovery. The therapeutic effects of one such plant product, n-butylidenephthalide (BP), are wide-ranging in nature, including impacts on cancer cell apoptosis, cell cycle arrest, and cancer cell senescence...
January 30, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29371604/swell1-is-a-glucose-sensor-regulating-%C3%AE-cell-excitability-and-systemic-glycaemia
#8
Chen Kang, Litao Xie, Susheel K Gunasekar, Anil Mishra, Yanhui Zhang, Saachi Pai, Yiwen Gao, Ashutosh Kumar, Andrew W Norris, Samuel B Stephens, Rajan Sah
Insulin secretion is initiated by activation of voltage-gated Ca2+ channels (VGCC) to trigger Ca2+-mediated insulin vesicle fusion with the β-cell plasma membrane. The firing of VGCC requires β-cell membrane depolarization, which is regulated by a balance of depolarizing and hyperpolarizing ionic currents. Here, we show that SWELL1 mediates a swell-activated, depolarizing chloride current (ICl,SWELL) in both murine and human β-cells. Hypotonic and glucose-stimulated β-cell swelling activates SWELL1-mediated ICl,SWELL and this contributes to membrane depolarization and activation of VGCC-dependent intracellular calcium signaling...
January 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29368845/cutaneous-lupus-erythematosus-clinico-pathologic-correlation
#9
Raffaele Filotico, Valentina Mastrandrea
Cutaneous lupus erythematosus (CLE) is a chronic-relapsing disease. It is defined as a LE localized to the skin without any significant systemic symptoms. Its annual incidence is of 4 cases per 100,000 persons with a prevalence of 73 cases per 100,000 persons. The etiology is unknown but it is considered as a prototype of autoimmune disease in which genetic factors (HLA), environmental factors (photo exposure and cigarette smoking) and pharmacological agents play an important role. The most accepted classification includes three clinical variants: acute (ACLE), subacute (SCLE) and chronic (CCLE)...
January 24, 2018: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/29321927/pulmonary-nocardiosis-in-a-patient-with-idiopathic-cd4-t-lymphocytopenia
#10
Vivek Jayaschandran, Sandra Gjorgova-Gjeorgjievski, Haamid Siddique
Idiopathic CD4 T-lymphocytopenia (ICL) is a rare immunodeficiency characterized by low CD4 T-lymphocyte count, which usually manifests with opportunistic infections. Nocardia as an opportunistic pathogen infecting patients with this condition has rarely been reported. Here, we describe the case of a 46-year-old male who presented with lung mass and respiratory and systemic symptoms and was eventually diagnosed with pulmonary nocardiosis. A workup for predisposing immunodeficiencies suggested a picture of ICL...
February 2018: Respirology Case Reports
https://www.readbyqxmd.com/read/29306471/correlation-between-frequency-domain-optical-coherence-tomography-and-fractional-flow-reserve-in-angiographically-intermediate-coronary-lesions
#11
Francesco Burzotta, Roberto Nerla, Jonathan Hill, Lazzaro Paraggio, Antonio Maria Leone, Jonathan Byrne, Italo Porto, Giampaolo Niccoli, Cristina Aurigemma, Carlo Trani, Philip MacCarthy, Filippo Crea
BACKGROUND: The decision-making process of patients with angiographically-intermediate coronary lesions (ICL) is clinically challenging and may benefit from adjunctive invasive techniques. Fractional-flow-reserve (FFR) represents the gold standard to evaluate ICL but frequency-domain optical-coherence-tomography (OCT) is a novel, promising, high resolution coronary imaging technique, which allows physiopathologic assessment of coronary plaque. We investigated the possible relation between OCT and FFR in selected ICL patients...
February 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29273016/buffering-zone-of-implantable-collamer-lens-sizing-in-v4c
#12
Seung Wan Nam, Dong Hui Lim, Joo Hyun, Eui-Sang Chung, Tae-Young Chung
BACKGROUND: The purpose of this study was to identify factors related to the unexpected vault in V4c implantable collamer lens (ICL; STAAR Surgical) implantation. METHODS: V4c ICLs were implanted in 43 eyes of 43 patients for the correction of myopia. The implanted V4c ICL sizes were determined individually with our previous V4 ICL sizing nomogram based on the sulcus-to-sulcus diameter (STS), and the V4 ICL sizes were then converted to V4c ICL sizes with a size-converting table...
December 22, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/29247884/a-low-toxicity-dna-alkylating-n-mustard-quinoline-conjugate-with-preferential-sequence-specificity-exerts-potent-antitumor-activity-against-colorectal-cancer
#13
Tai-Lin Chen, Yi-Wen Lin, Yan-Bo Chen, Jing-Jer Lin, Tsann-Long Su, Chia-Ning Shen, Te-Chang Lee
Efficacy and safety are fundamental prerequisites for anticancer drug development. In the present study, we explored the anti-colorectal cancer (CRC) activity of SL-1, a DNA-directed N-mustard-quinoline conjugate. The N-mustard moiety in SL-1 induced DNA strand breaks, interstrand cross-links (ICLs), G2/M arrest, and apoptosis, whereas its quinoline moiety preferentially directed SL-1 to target the selective guanine sequence 5'-G-G/C-N-G-C/T-3'. Notably, SL-1 was highly cytotoxic to various CRC cell lines. Experiments using xenograft models revealed that SL-1 was more potent than 5-fluorouracil (5-FU) and oxaliplatin for suppressing the growth of RKO and RKO-E6 (oxaliplatin-resistant subline) cells as well as metastatic SW620 cells...
December 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29245857/interband-cascade-laser-based-mid-infrared-methane-sensor-system-using-a-novel-electrical-domain-self-adaptive-direct-laser-absorption-spectroscopy-sa-dlas
#14
Fang Song, Chuantao Zheng, Wanhong Yan, Weilin Ye, Yiding Wang, Frank K Tittel
To suppress sensor noise with unknown statistical properties, a novel self-adaptive direct laser absorption spectroscopy (SA-DLAS) technique was proposed by incorporating a recursive, least square (RLS) self-adaptive denoising (SAD) algorithm and a 3291 nm interband cascade laser (ICL) for methane (CH4) detection. Background noise was suppressed by introducing an electrical-domain noise-channel and an expectation-known-based RLS SAD algorithm. Numerical simulations and measurements were carried out to validate the function of the SA-DLAS technique by imposing low-frequency, high-frequency, White-Gaussian and hybrid noise on the ICL scan signal...
December 11, 2017: Optics Express
https://www.readbyqxmd.com/read/29234069/the-human-dna-glycosylases-neil1-and-neil3-excise-psoralen-induced-dna-dna-cross-links-in-a-four-stranded-dna-structure
#15
Peter R Martin, Sophie Couvé, Caroline Zutterling, Mustafa S Albelazi, Regina Groisman, Bakhyt T Matkarimov, Jason L Parsons, Rhoderick H Elder, Murat K Saparbaev
Interstrand cross-links (ICLs) are highly cytotoxic DNA lesions that block DNA replication and transcription by preventing strand separation. Previously, we demonstrated that the bacterial and human DNA glycosylases Nei and NEIL1 excise unhooked psoralen-derived ICLs in three-stranded DNA via hydrolysis of the glycosidic bond between the crosslinked base and deoxyribose sugar. Furthermore, NEIL3 from Xenopus laevis has been shown to cleave psoralen- and abasic site-induced ICLs in Xenopus egg extracts. Here we report that human NEIL3 cleaves psoralen-induced DNA-DNA cross-links in three-stranded and four-stranded DNA substrates to generate unhooked DNA fragments containing either an abasic site or a psoralen-thymine monoadduct...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29223238/pupillary-block-glaucoma-secondary-to-central-port-occlusion-following-insertion-of-a-phakic-implantable-copolymer-lens
#16
Felix Gonzalez-Lopez, Rafael Bilbao-Calabuig, Ricardo Alen, Blas Mompean
A 28-year-old woman had uneventful implantation of a phakic intraocular lens (pIOL) in her left eye (Visian ICL, EVO+ model, 13.2, -7.50 diopters) to correct myopia. Six days after the procedure, she presented with herniation of the iris. Surgical reduction was carried out successfully through the previous peripheral corneal paracentesis. On the following day, the patient reported ocular pain and blurry vision. Examination showed a shallow anterior chamber, moderate diffuse corneal edema, and ocular hypertension...
November 2017: Journal of Cataract and Refractive Surgery
https://www.readbyqxmd.com/read/29157227/metabolic-adaptation-of-two-in-silico-mutants-of-mycobacterium-tuberculosis-during-infection
#17
Víctor A López-Agudelo, Andres Baena, Howard Ramirez-Malule, Silvia Ochoa, Luis F Barrera, Rigoberto Ríos-Estepa
BACKGROUND: Up to date, Mycobacterium tuberculosis (Mtb) remains as the worst intracellular killer pathogen. To establish infection, inside the granuloma, Mtb reprograms its metabolism to support both growth and survival, keeping a balance between catabolism, anabolism and energy supply. Mtb knockouts with the faculty of being essential on a wide range of nutritional conditions are deemed as target candidates for tuberculosis (TB) treatment. Constraint-based genome-scale modeling is considered as a promising tool for evaluating genetic and nutritional perturbations on Mtb metabolic reprogramming...
November 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29156999/risk-factors-for-intracranial-lesions-and-mortality-in-older-patients-with-mild-traumatic-brain-injuries
#18
Ma Angustias Ibañez Pérez De La Blanca, Enrique Fernández Mondéjar, Francisco Javier Gómez Jimènez, Jóse María Alonso Morales, Ma Dolores Quijano Lombardo, Juan Luis Viso Rodriguez
PRIMARY OBJECTIVE: To identify risk factors for intracerebral lesion (ICL) in older adults with mild traumatic brain injury (MTBI) and evaluate the influence of comorbidities on outcomes. RESEARCH DESIGN: Prospective cohort study. METHODS AND PROCEDURES: Information was gathered on clinical history/examination, cranial computed tomography, admission Glasgow Coma Scale (GCS) score, analytical and coagulation findings, and mortality at 1 week post-discharge...
2018: Brain Injury: [BI]
https://www.readbyqxmd.com/read/29138321/in-vivo-bioluminescence-imaging-of-labile-iron-accumulation-in-a-murine-model-of-acinetobacter-baumannii-infection
#19
Allegra T Aron, Marie C Heffern, Zachery R Lonergan, Mark N Vander Wal, Brian R Blank, Benjamin Spangler, Yaofang Zhang, Hyo Min Park, Andreas Stahl, Adam R Renslo, Eric P Skaar, Christopher J Chang
Iron is an essential metal for all organisms, yet disruption of its homeostasis, particularly in labile forms that can contribute to oxidative stress, is connected to diseases ranging from infection to cancer to neurodegeneration. Iron deficiency is also among the most common nutritional deficiencies worldwide. To advance studies of iron in healthy and disease states, we now report the synthesis and characterization of iron-caged luciferin-1 (ICL-1), a bioluminescent probe that enables longitudinal monitoring of labile iron pools (LIPs) in living animals...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29137116/altering-residue-134-confers-an-increased-substrate-range-of-alkylated-nucleosides-to-the-e-coli-ogt-protein
#20
Nadia M Schoonhoven, Derek K O'Flaherty, Francis P McManus, Lauralicia Sacre, Anne M Noronha, M Judith Kornblatt, Christopher J Wilds
O⁶-Alkylguanine-DNA alkyltransferases (AGTs) are proteins responsible for the removal of mutagenic alkyl adducts at the O⁶-atom of guanine and O⁴-atom of thymine. In the current study we set out to understand the role of the Ser134 residue in the Escherichia coli AGT variant OGT on substrate discrimination. The S134P mutation in OGT increased the ability of the protein to repair both O⁶-adducts of guanine and O⁴-adducts of thymine. However, the S134P variant was unable, like wild-type OGT, to repair an interstrand cross-link (ICL) bridging two O⁶-atoms of guanine in a DNA duplex...
November 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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