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https://www.readbyqxmd.com/read/29471585/ripply3-is-required-for-the-maintenance-of-epithelial-sheets-in-the-morphogenesis-of-pharyngeal-pouches
#1
Yoshihiro Tsuchiya, Yusuke Mii, Kazunori Okada, Mikio Furuse, Tadashi Okubo, Shinji Takada
During tissue development, the morphogenesis of epithelial sheets is regulated by many factors, including mechanical force, although the underlying mechanisms remain largely unknown. In the pharyngeal region of the vertebrate embryo, endodermal epithelium is reiteratively folded outward to form pharyngeal pouches, making partitions between the pharyngeal arches. Ripply3, encoding a member of the Ripply family of adaptor proteins, is required for the pouch formation posterior to the 2nd pharyngeal pouch. In this study, we found that the expression of mouse Ripply3 was specifically activated in accordance with the bending of the endodermal epithelium during the pouch formation...
February 22, 2018: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/29471489/the-h-subunit-of-the-restriction-endonuclease-cgli-contains-a-prototype-dead-z1-helicase-like-motor
#2
Paulius Toliusis, Giedre Tamulaitiene, Rokas Grigaitis, Donata Tuminauskaite, Arunas Silanskas, Elena Manakova, Ceslovas Venclovas, Mark D Szczelkun, Virginijus Siksnys, Mindaugas Zaremba
CglI is a restriction endonuclease from Corynebacterium glutamicum that forms a complex between: two R-subunits that have site specific-recognition and nuclease domains; and two H-subunits, with Superfamily 2 helicase-like DEAD domains, and uncharacterized Z1 and C-terminal domains. ATP hydrolysis by the H-subunits catalyses dsDNA translocation that is necessary for long-range movement along DNA that activates nuclease activity. Here, we provide biochemical and molecular modelling evidence that shows that Z1 has a fold distantly-related to RecA, and that the DEAD-Z1 domains together form an ATP binding interface and are the prototype of a previously undescribed monomeric helicase-like motor...
February 20, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29471486/selection-of-hyperproduction-of-ampc-and-sme-1-in-a-carbapenem-resistant-serratia-marcescens-isolate-during-antibiotic-therapy
#3
Peera Hemarajata, Thomas Amick, Shangxin Yang, Aric Gregson, Cameron Holzmeyer, Karen Bush, Romney M Humphries
Objectives: Antibiotic selective pressure may result in changes to antimicrobial susceptibility throughout the course of infection, especially for organisms that harbour chromosomally encoded AmpC β-lactamases, notably Enterobacter spp., in which hyperexpression of ampC may be induced following treatment with cephalosporins. In this study, we document a case of bacteraemia caused by a blaSME-1-harbouring Serratia marcescens that subsequently developed resistance to expanded-spectrum cephalosporins, piperacillin/tazobactam and fluoroquinolones, over the course of several months of treatment with piperacillin/tazobactam and ciprofloxacin...
February 19, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29471464/poor-immunogenicity-not-vaccine-strain-egg-adaptation-may-explain-the-low-h3n2-influenza-vaccine-effectiveness-in-2012-13
#4
Sarah Cobey, Sigrid Gouma, Kaela Parkhouse, Benjamin S Chambers, Hildegund C Ertl, Kenneth E Schmader, Rebecca A Halpin, Xudong Lin, Timothy B Stockwell, Suman R Das, Emily Landon, Vera Tesic, Ilan Youngster, Benjamin A Pinsky, David E Wentworth, Scott E Hensley, Yonatan H Grad
Background: Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza strains and to the vaccine's elicitation of protective immunity in only a subset of the population. The low H3N2 VE in the 2012-2013 season was attributed to egg-adaptive mutations that created antigenic mismatch between the actual vaccine strain (IVR-165) and both the intended vaccine strain (A/Victoria/361/2011) and the predominant circulating strains (clades 3C...
February 20, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29471435/immune-infiltration-in-invasive-lobular-breast-cancer
#5
Christine Desmedt, Roberto Salgado, Marco Fornili, Giancarlo Pruneri, Gert Van den Eynden, Gabriele Zoppoli, Françoise Rothé, Laurence Buisseret, Soizic Garaud, Karen Willard-Gallo, David Brown, Yacine Bareche, Ghizlane Rouas, Christine Galant, François Bertucci, Sherene Loi, Giuseppe Viale, Angelo Di Leo, Andrew R Green, Ian O Ellis, Emad A Rakha, Denis Larsimont, Elia Biganzoli, Christos Sotiriou
Background: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC. Methods: We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC)...
February 20, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29471425/foxl2c134w-induced-cyp19-expression-via-cooperation-with-smad3-in-hgrc1-cells
#6
Martina Belli, Nahoko Iwata, Tomoko Nakamura, Akira Iwase, Dwayne Stupack, Shunichi Shimasaki
Germline knockout studies in female mice demonstrated an essential role for FOXL2 in early follicle development, while an inducible granulosa cell (GC) specific deletion of Foxl2 in adults has shown ovary-to-testis somatic sex reprogramming. In women, over 120 different germline mutations in the FOXL2 gene have been shown to cause blepharophimosis/ptosis/epicantus inversus syndrome associated with or without primary ovarian insufficiency. By contrast, a single somatic mutation (FOXL2C134W) accounts for almost all adult-type GC tumors (aGCTs)...
February 19, 2018: Endocrinology
https://www.readbyqxmd.com/read/29471358/eif4a-alleviates-the-translational-repression-mediated-by-classical-secondary-structures-more-than-by-g-quadruplexes
#7
Joseph A Waldron, Farheen Raza, John Le Quesne
Increased activity of the mRNA helicase eIF4A drives cellular malignancy by reprogramming cellular translation, and eIF4A activity is the direct or indirect target of many emerging cancer therapeutics. The enriched presence of (GGC)4 motifs, which have the potential to fold into two-layered G-quadruplexes, within the 5'UTRs of eIF4A-dependent mRNAs suggests that eIF4A is required for the unwinding of these structures within these eIF4A-controlled mRNAs. However, the existence of folded G-quadruplexes within cells remains controversial, and G-quadruplex folding is in direct competition with classical Watson-Crick based secondary structures...
February 19, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29471263/predictive-models-for-tyrosinase-inhibitors-challenges-from-heterogeneous-activity-data-determined-by-different-experimental-protocols
#8
Haifeng Tang, Fengchao Cui, Lunyang Liu, Yunqi Li
Quantitative Structure-Activity Relationship (QSAR) models of tyrosinase inhibitors were built using Random Forest (RF) algorithm and evaluated by the out-of-bag estimation (R2 OOB ) and 10-fold cross validation (Q2 CV ). We found that the performances of QSAR models were closely correlated with the systematic errors of inhibitory activities of tyrosinase inhibitors arising from the different measuring protocols. By defining ERRsys , outliers with larger errors can be efficiently identified and removed from heterogeneous activity data...
February 13, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29471160/persistent-first-intersegmental-artery-pfia-visualized-by-three-dimensional-computed-tomography-angiography-in-chinese-population
#9
Haocong Zhang, Wei Chai, Shuang Wang, Yan Wang, Hongwei Li
BACKGROUND: Persistent first intersegmental artery (PFIA) is one of the most frequently vertebral artery (VA) variations. The presence of PFIA obviously increases the complexity and difficulty of vertebral lesion treatment. Thus, preoperative detection of PFIA is necessary to increase the successful rate of surgeries. We attempted to evaluate the utility value of three-dimension (3D) computed tomography angiography (CTA) for detecting PFIA in the north Chinese population. MATERIALS AND METHODS: Consecutive patients subjected to CTA between June 2012 and March 2014 were recruited from 5 clinical centers in the north of China...
February 19, 2018: International Journal of Surgery
https://www.readbyqxmd.com/read/29471144/intestinal-absorption-and-activation-of-decitabine-amino-acid-ester-prodrugs-mediated-by-peptide-transporter-pept1-and-enterocyte-enzymes
#10
Wenhui Tao, Dongyang Zhao, Mengchi Sun, Ziyu Wang, Bin Lin, Yu Bao, Yingying Li, Zhonggui He, Yinghua Sun, Jin Sun
Decitabine (DAC), a potent DNA methyltransferase (DNMT) inhibitor, has a limited oral bioavailability. Its 5'-amino acid ester prodrugs could improve its oral delivery but the specific absorption mechanism is not yet fully understood. The aim of this present study was to investigate the in vivo absorption and activation mechanism of these prodrugs using in situ intestinal perfusion and pharmacokinetics studies in rats. Although PEPT1 transporter is pH dependent, there appeared to be no proton cotransport in the perfusion experiment with a preferable transport at pH 7...
February 19, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29471121/diamine-and-pegylated-diamine-conjugates-of-triterpenic-acids-as-potential-anticancer-agents
#11
Marta Medina-O'Donnell, Francisco Rivas, Fernando J Reyes-Zurita, Antonio Martinez, Jose A Lupiañez, Andres Parra
A set of 18 amide derivatives of oleanolic or maslinic acid has been semi-synthesised. Twelve were diamine conjugates at C-28 of these triterpenic acids and the other six were PEGylated-diamine derivatives. The cytotoxic effects of these 18 triterpenic derivatives in three cancer-cell lines (B16-F10, HT29, and Hep G2) have been assayed, and have been compared to three non-tumour cell lines of the same or a similar tissue (HPF, IEC-18, and WRL68). The cell viability percentages for the non-tumour HPF line for almost all diamine conjugates of the tested triterpenic acids ranged from 81% to 94%...
February 16, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29471083/imaging-the-penetration-and-distribution-of-zinc-and-zinc-species-after-topical-application-of-zinc-pyrithione-to-human-skin
#12
Amy M Holmes, Ivan Kempson, Tyron Turnbull, David Paterson, Michael S Roberts
Zinc pyrithione is an active component incorporated in an extensive range of topically applied commercial products that are used worldwide. Despite its prevalence, no published study has investigated the penetration of zinc from the zinc pyrithione complex into human skin. Zinc is crucial for healthy skin function however an elevated concentration of labile zinc is toxic outside a narrow concentration range. Synchrotron X-ray fluorescence microscopy in conjunction with X-ray absorption near edge structure spectroscopy was used to map the deposition of zinc, quantitate the amount of zinc within the skin and to identify a change in the chemical form of zinc after application...
February 19, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29471044/engineered-protein-degradation-of-farnesyl-pyrophosphate-synthase-is-an-effective-regulatory-mechanism-to-increase-monoterpene-production-in-saccharomyces-cerevisiae
#13
Bingyin Peng, Lars K Nielsen, Sotirios C Kampranis, Claudia E Vickers
Monoterpene production in Saccharomyces cerevisae requires the introduction of heterologous monoterpene synthases (MTSs). The endogenous farnesyl pyrosphosphate synthase (FPPS; Erg20p) competes with MTSs for the precursor geranyl pyrophosphate (GPP), which limits the production of monoterpenes. ERG20 is an essential gene that cannot be deleted and transcriptional down-regulation of ERG20 has failed to improve monoterpene production. Here, we investigated an N-degron-dependent protein degradation strategy to down-regulate Erg20p activity...
February 19, 2018: Metabolic Engineering
https://www.readbyqxmd.com/read/29470977/the-unfolded-protein-response-in-ischemic-heart-disease
#14
REVIEW
Xiaoding Wang, Lin Xu, Thomas G Gillette, Xuejun Jiang, Zhao V Wang
Ischemic heart disease is a severe stress condition that causes extensive pathological alterations and triggers cardiac cell death. Accumulating evidence suggests that the unfolded protein response (UPR) is strongly induced by myocardial ischemia. The UPR is an evolutionarily conserved cellular response to cope with protein-folding stress, from yeast to mammals. Endoplasmic reticulum (ER) transmembrane sensors detect the accumulation of unfolded proteins and stimulate a signaling network to accommodate unfolded and misfolded proteins...
February 19, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29470949/amputation-of-a-c-terminal-helix-of-the-%C3%AE-subunit-increases-atp-hydrolysis-activity-of-cyanobacterial-f-1-atp-synthase
#15
Kumiko Kondo, Yu Takeyama, Ei-Ichiro Sunamura, Yuka Madoka, Yuki Fukaya, Atsuko Isu, Toru Hisabori
F1 is a soluble part of Fo F1 -ATP synthase and performs a catalytic process of ATP hydrolysis and synthesis. The γ subunit, which is the rotary shaft of F1 motor, is composed of N-terminal and C-terminal helices domains, and a protruding Rossman-fold domain located between the two major helices parts. The N-terminal and C-terminal helices domains of γ assemble into an antiparallel coiled-coil structure, and are almost embedded into the stator ring composed of α3 β3 hexamer of the F1 molecule. Cyanobacterial and chloroplast γ subunits harbor an inserted sequence of 30 or 39 amino acids length within the Rossman-fold domain in comparison with bacterial or mitochondrial γ...
February 19, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29470934/bivalent-oral-cholera-vaccine-in-participants-aged-1-year-and-older-in-the-dominican-republic-a-phase-iii-single-arm-safety-and-immunogenicity-trial
#16
Lina Cordero De Los Santos, Jesús Feris-Iglesias, Naveena Aloysia D'Cor, Venkata Jayanth Midde, Badri Narayan Patnaik, Yaël Thollot, Anvar Rasuli, Eric Desauziers
The Dominican Republic, historically non-endemic for cholera, is experiencing an ongoing cholera epidemic. We assessed the safety and immunogenicity of two doses of the killed bivalent (O1 and O139) whole-cell oral cholera vaccine (OCV) on day (D)0 and D14 in healthy participants aged ≥1 year. Immediate unsolicited systemic adverse events (AEs) were monitored up to 30 minutes and solicited systemic reactions, up to 7 days after each vaccination. Unsolicited AEs were recorded up to D14 (post-dose 1) and 30 days post-dose 2...
February 22, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29470842/elucidating-the-nature-of-the-excited-state-of-a-heteroleptic-copper-photosensitizer-using-time-resolved-x-ray-absorption-spectroscopy
#17
Dooshaye Moonshiram, Pablo Garrido-Barros, Carolina Gimbert-Suriñach, Antonio Picon, Cunming Liu, Xiaoyi Zhang, Michael Karnahl, Antoni Llobet
We report the light-induced electronic and geometric changes taking place within a heteroleptic Cu(I) photosensitizer, namely [(xant)Cu(Me2phenPh2)]PF6 (xant = xantphos, Me2phenPh2 = bathocuproine), by time-resolved X-ray absorption spectroscopy in the ps-µs time-regime. Time-resolved X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analysis enabled the elucidation of the electronic and structural configuration of the copper centre in the excited state as well as its decay dynamics in different solvent conditions with and without triethylamine acting as a sacrificial electron donor...
February 22, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29470829/enhancing-the-therapeutic-efficacy-of-tamoxifen-citrate-loaded-span-based-nano-vesicles-on-human-breast-adenocarcinoma-cells
#18
Mohammed A Kassem, Mohamed A Megahed, Sherif K Abu Elyazid, Fathy I Abd-Allah, Tamer M Abdelghany, Ahmed M Al-Abd, Khalid M El-Say
Serious adverse effects and low selectivity to cancer cells are the main obstacles of long term therapy with Tamoxifen (Tmx). This study aimed to develop Tmx-loaded span-based nano-vesicles for delivery to malignant tissues with maximum efficacy. The effect of three variables on vesicle size (Y1 ), zeta potential (Y2 ), entrapment efficiency (Y3 ) and the cumulative percent release after 24 h (Y4 ) were optimized using Box-Behnken design. The optimized formula was prepared and tested for its stability in different storage conditions...
February 22, 2018: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29470707/modeling-simulation-and-employing-dilution-dialysis-microfluidic-chip-ddmc-for-heightening-proteins-refolding-efficiency
#19
F Kashanian, M M Masoudi, A Shamloo, M Habibi-Rezaei, A A Moosavi-Movahedi
Miniaturized systems based on the principles of microfluidics are widely used in various fields, such as biochemical and biomedical applications. Systematic design processes are demanded the proper use of these microfluidic devices based on mathematical simulations. Aggregated proteins (e.g., inclusion bodies) in solution with chaotropic agents (such as urea) at high concentration in combination with reducing agents are denatured. Refolding methods to achieve the native proteins from inclusion bodies of recombinant protein relying on denaturant dilution or dialysis approaches for suppressing protein aggregation is very important in the industrial field...
February 22, 2018: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/29470593/increased-gi-protein-signaling-potentiates-the-negative-chronotropic-effect-of-adenosine-in-the-shr-right-atrium
#20
Juliano Q D Rodrigues, Henrique Camara, Aron Jurkiewicz, Rosely O Godinho
Hypertension is a risk factor for cardiovascular diseases, which have been associated with dysfunction of sympathetic and purinergic neurotransmission. Therefore, herein, we evaluated whether modifications of adenosine receptor signaling may contribute to the cardiac dysfunction observed in hypertension. Isolated right atria from spontaneously hypertensive (SHR) or normotensive Wistar rats (NWR) were used to investigate the influence of adenosine receptor signaling cascade in the cardiac chronotropism. Our results showed that adenosine, the endogenous agonist of adenosine receptors, and CPA, a selective agonist of A1 receptor, decreased the atrial chronotropism of NWR and SHR in a concentration- and time-dependent manner, culminating in cardiac arrest (0 bpm)...
February 22, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
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