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https://www.readbyqxmd.com/read/28087633/the-abl-pathway-bifurcates-to-balance-enabled-and-rac-signaling-in-axon-patterning-in-drosophila
#1
Ramakrishnan Kannan, Jeong-Kuen Song, Tatiana Karpova, Akanni Clarke, Madhuri Shivalkar, Benjamin Wang, Lyudmila Kotlyanskaya, Irina Kuzina, Qun Gu, Edward Giniger
The Abl tyrosine kinase signaling network controls cell migration, epithelial organization, axon patterning and other aspects of development. While individual components are known, the relationships among them remain mysterious. We now use FRET measurements of pathway activity, analysis of protein localization and genetic epistasis to dissect the structure of this network in Drosophila We find that the adaptor protein Disabled stimulates Abl kinase activity. Abl suppresses the actin regulatory factor Enabled, and we find that Abl also acts through the GEF Trio to stimulate the signaling activity of Rac GTPase: Abl gates the activity of the spectrin repeats of Trio, allowing them to relieve intramolecular repression of Trio GEF activity by the Trio N-terminal domain...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28086938/alpha-enolase-eno1-controls-alpha-v-beta-3-integrin-expression-and-regulates-pancreatic-cancer-adhesion-invasion-and-metastasis
#2
Moitza Principe, Simone Borgoni, Mariafrancesca Cascione, Michelle Samuel Chattaragada, Sammy Ferri-Borgogno, Michela Capello, Sara Bulfamante, Jennifer Chapelle, Francesca Di Modugno, Paola Defilippi, Paola Nisticò, Paola Cappello, Chiara Riganti, Stefano Leporatti, Francesco Novelli
BACKGROUND: We have previously shown that in pancreatic ductal adenocarcinoma (PDA) cells, the glycolytic enzyme alpha-enolase (ENO1) also acts as a plasminogen receptor and promotes invasion and metastasis formation. Moreover, ENO1 silencing in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibody inhibits PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28074221/exploring-the-thermostable-properties-of-halohydrin-dehalogenase-from-agrobacterium-radiobacter-ad1-by-a-combinatorial-directed-evolution-strategy
#3
Zhiyun Wu, Wenfeng Deng, Yapei Tong, Qian Liao, Dongmin Xin, Huashun Yu, Juan Feng, Lixia Tang
As a crucial factor for biocatalysts, protein thermostability often arises from a combination of factors that are often difficult to rationalize. In this work, the thermostable nature of halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) was systematically explored using a combinatorial directed evolution approach. For this, a mutagenesis library of HheC mutants was first constructed using error-prone PCR with low mutagenesis frequency. After screening approximately 2000 colonies, six mutants with eight mutation sites were obtained...
January 10, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28070992/molecular-signal-networks-and-regulating-mechanisms-of-the-unfolded-protein-response
#4
Jing Gong, Xing-Zhi Wang, Tao Wang, Jiao-Jiao Chen, Xiao-Yuan Xie, Hui Hu, Fang Yu, Hui-Lin Liu, Xing-Yan Jiang, Han-Dong Fan
Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum (ER). One of the primary mechanisms is the unfolded protein response (UPR). In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein (BiP) interacts with the three sensors (protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1α (IRE1α))...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28067917/structural-insights-into-a-unique-hsp70-hsp40-interaction-in-the-eukaryotic-ribosome-associated-complex
#5
Felix Alexander Weyer, Andrea Gumiero, Genís Valentín Gesé, Karine Lapouge, Irmgard Sinning
Cotranslational chaperones assist de novo folding of nascent polypeptides, prevent them from aggregating and modulate translation. The ribosome-associated complex (RAC) is unique in that the Hsp40 protein Zuo1 and the atypical Hsp70 chaperone Ssz1 form a stable heterodimer, which acts as a cochaperone for the Hsp70 chaperone Ssb. Here we present the structure of the Chaetomium thermophilum RAC core comprising Ssz1 and the Zuo1 N terminus. We show how the conserved allostery of Hsp70 proteins is abolished and this Hsp70-Hsp40 pair is molded into a functional unit...
January 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28067313/redundant-functions-of-i-bar-family-members-irsp53-and-irtks-are-essential-for-embryonic-development
#6
Ai Mei Chou, Kai Ping Sem, Wei Jun Lam, Sohail Ahmed, Chin Yan Lim
The insulin receptor substrate of 53 kDa, IRSp53, is an adaptor protein that works with activated GTPases, Cdc42 and Rac, to modulate actin dynamics and generate membrane protrusions in response to cell signaling. Adult mice that lack IRSp53 fail to regulate synaptic plasticity and exhibit hippocampus-associated learning deficiencies. Here, we show that 60% of IRSp53 null embryos die at mid to late gestation, indicating a vital IRSp53 function in embryonic development. We find that IRSp53 KO embryos displayed pleiotropic phenotypes such as developmental delay, oligodactyly and subcutaneous edema, and died of severely impaired cardiac and placental development...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062165/daboialectin-a-c-type-lectin-from-russell-s-viper-venom-induces-cytoskeletal-damage-and-apoptosis-in-human-lung-cancer-cells-in%C3%A2-vitro
#7
Jigni Pathan, Sukanta Mondal, Angshuman Sarkar, Dibakar Chakrabarty
'Daboialectin', a low molecular weight C-type lectin (18.5 kDa) isolated from Russell's viper venom showed cytotoxic effects on human broncho-alveolar carcinoma derived (A549) cell lines. Daboialectin induced inhibition of A549 cell growth was time and concentration dependent with severe morphological changes by altering the functions of small GTPases such as Rac, Rho and cdc42. ROS induced DNA damage may result in apoptosis by inducing disruption of membrane integrity, blebbing and nuclear disintegration by activating caspases...
January 3, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28061018/bronchopulmonary-pharmacokinetics-of-r-salbutamol-and-s-salbutamol-enantiomers-in-pulmonary-epithelial-lining-fluid-and-lung-tissue-of-horses
#8
Glenn A Jacobson, Sharanne Raidal, Kate Robson, Christian K Narkowicz, David S Nichols, E Haydn Walters
AIMS: Salbutamol is usually administered as a racemic mixture but little is known about the enantioselectivity of salbutamol pharmacokinetics in the lung. This study was designed to investigate enantiomer concentrations in lung tissue after inhaled dosing. METHODS: Horses (n = 12) received racemic (rac-) salbutamol 1000 microgram via inhalation. Enantioselective UPLC-MS/MS was used to determine salbutamol concentrations in pulmonary epithelial lining fluid (PELF) sampled 2, 5, 10 and 15 min after administration, in central lung (endoscopic bronchial biopsy) and peripheral lung (percutaneous pulmonary biopsy) tissues (at 20 and 25 minutes respectively), and in plasma samples...
January 6, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28060503/coordination-polymers-and-cage-containing-frameworks-in-uranyl-ion-complexes-with-rac-and-1r-2r-trans-1-2-cyclohexanedicarboxylates-consequences-of-chirality
#9
Pierre Thuéry, Jack Harrowfield
Racemic and enantiopure (1R,2R) forms of trans-1,2-cyclohexanedicarboxylic acid (H2chdc and R-H2chdc, respectively) have been used in the synthesis of a series of 13 uranyl ion complexes, all obtained under solvo-hydrothermal conditions and in the presence of additional metal cations and/or N-donor ligands. While the homometallic complex [UO2(R-chdc)] (1) was only obtained with the enantiopure ligand, complexes [UO2(chdc)(THF)] (2), [UO2(chdc)(DMF)] (3), and [UO2(chdc)(NMP)] (4), with a coordinated solvent molecule, were obtained from the racemic form only; all crystallize as two-dimensional (2D) assemblies...
January 6, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28057795/pleiotropic-effects-of-statins-on-the-cardiovascular-system
#10
REVIEW
Adam Oesterle, Ulrich Laufs, James K Liao
The statins have been used for 30 years to prevent coronary artery disease and stroke. Their primary mechanism of action is the lowering of serum cholesterol through inhibiting hepatic cholesterol biosynthesis thereby upregulating the hepatic low-density lipoprotein (LDL) receptors and increasing the clearance of LDL-cholesterol. Statins may exert cardiovascular protective effects that are independent of LDL-cholesterol lowering called pleiotropic effects. Because statins inhibit the production of isoprenoid intermediates in the cholesterol biosynthetic pathway, the post-translational prenylation of small GTP-binding proteins such as Rho and Rac, and their downstream effectors such as Rho kinase and nicotinamide adenine dinucleotide phosphate oxidases are also inhibited...
January 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28055191/chiral-recognition-and-dynamic-thermodynamic-resolution-of-sulfoxides-by-chiral-iridium-iii-complexes
#11
Su-Yang Yao, Xing-Yang Chen, Yan-Ling Ou, Bao-Hui Ye
The optically active Ir(III) complex Λ-[Ir(ppy)2(MeCN)2](PF6) (ppy is 2-phenylpyridine) with a chiral-at-metal was first demonstrated to preferentially react with (R)-configuration sulfoxides 2-(alkylsulfinyl)phenol (HLO-R, R = Me, Et, (i)Pr, and Bn) rather than (S)-configuration sulfoxides under thermodynamic equilibrium due to the hydrogen-bonding interaction and the differences in the steric interference, and thus act as a highly efficient enantioreceptor for resolution of sulfoxide enatiomers. Treatment of Λ-[Ir(ppy)2(MeCN)2](PF6) with 2 equiv of rac-HLO-R offered (S)-HLO-R in yields of 46-47% with 97-99% enantiomeric excess (ee) values and Λ-[Ir(ppy)2{(S)-LO-R}] complex in yields of 89-93% with 98% diastereomeric excess (de)...
January 5, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28054763/islet-amyloid-polypeptide-membrane-interactions-effects-of-membrane-composition
#12
Xiaoxue Zhang, Johnna R St Clair, Erwin London, Daniel P Raleigh
Amyloid formation by islet amyloid polypeptide (IAPP) contributes to β-cell dysfunction in type 2 diabetes. Perturbation of the β-cell membrane may contribute to IAPP-induced toxicity. We examine the effects of lipid composition, salt, and buffer on IAPP amyloid formation and on the ability of IAPP to induce leakage of model membranes. Even low levels of anionic lipids promote amyloid formation and membrane permeabilization. Increasing the percentage of the anionic lipids, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS) or 1,2-dioleoyl-sn-glycero-3-phospho(1'-rac-glycerol), enhances the rate of amyloid formation and increases the level of membrane permeabilization...
January 5, 2017: Biochemistry
https://www.readbyqxmd.com/read/28051998/prex1-integrates-g-protein-coupled-receptor-and-phosphoinositide-3-kinase-signaling-to-promote-glioblastoma-invasion
#13
Alexander Gont, Manijeh Daneshmand, John Woulfe, Sylvie J Lavictoire, Ian A J Lorimer
A defining feature of the brain cancer glioblastoma is its highly invasive nature. When glioblastoma cells are isolated from patients using serum free conditions, they accurately recapitulate this invasive behaviour in animal models. The Rac subclass of Rho GTPases has been shown to promote invasive behaviour in glioblastoma cells isolated in this manner. However the guanine nucleotide exchange factors responsible for activating Rac in this context have not been characterized previously. PREX1 is a Rac guanine nucleotide exchange factor that is synergistically activated by binding of G protein αγ subunits and the phosphoinositide 3-kinase pathway second messenger phosphatidylinositol 3,4,5 trisphosphate...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28051852/artificial-slanted-nanocilia-array-as-a-mechanotransducer-for-controlling-cell-polarity
#14
Hong Nam Kim, Kyung-Jin Jang, Jung-Youn Shin, Daeshik Kang, Sang Moon Kim, Ilkyoo Koh, Yoonmi Hong, Segeun Jang, Min Sung Kim, Byung-Soo Kim, Hoon Eui Jeong, Noo Li Jeon, Pilnam Kim, Kahp-Yang Suh
We present a method to induce cell directional behavior using slanted nanocilia arrays. NIH-3T3 fibroblasts demonstrated bidirectional polarization in a rectangular arrangement on vertical nanocilia arrays and exhibited a transition from a bidirectional to a unidirectional polarization pattern when the angle of the nanocilia was decreased from 90° to 30°. The slanted nanocilia guided and facilitated spreading by allowing the cells to contact the sidewalls of the nanocilia, and the directional migration of the cells opposed the direction of the slant due to the anisotropic bending stiffness of the slanted nanocilia...
January 4, 2017: ACS Nano
https://www.readbyqxmd.com/read/28051168/mechanisms-of-yersinia-yopo-kinase-substrate-specificity
#15
Wei Lin Lee, Pavithra Singaravelu, Sheena Wee, Bo Xue, Khay Chun Ang, Jayantha Gunaratne, Jonathan M Grimes, Kunchithapadam Swaminathan, Robert C Robinson
Yersinia bacteria cause a range of human diseases, including yersiniosis, Far East scarlet-like fever and the plague. Yersiniae modulate and evade host immune defences through injection of Yersinia outer proteins (Yops) into phagocytic cells. One of the Yops, YopO (also known as YpkA) obstructs phagocytosis through disrupting actin filament regulation processes - inhibiting polymerization-promoting signaling through sequestration of Rac/Rho family GTPases and by using monomeric actin as bait to recruit and phosphorylate host actin-regulating proteins...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28046162/effect-of-ractopamine-hydrochloride-optaflexx-dose-and-duration-on-growth-performance-and-carcass-characteristics-of-finishing-steers
#16
C J Bittner, G I Crawford, L L Berger, S Holt, R R Pritchard, W J Platter, M T Van Koevering, N A Pyatt, G E Erickson
Three experiments evaluated the effects of ractopamine hydrochloride (RAC) dose and duration on growth performance and carcass characteristics of feedlot steers. In total, 1,509 crossbred steers (530 kg initial BW [SD 22]) were used in a randomized complete block design using a 3 × 3 factorial treatment structure. Treatments consisted of RAC dose (0, 100, or 200 mg/steer daily) and duration (28, 35, or 42 d) of RAC feeding prior to harvest. Initiation of RAC dose was staggered (7 d apart) based on RAC duration, which resulted in common days on feed among treatments...
December 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/28038319/recruitment-of-tiam1-to-semaphorin-4d-activates-rac-and-enhances-proliferation-invasion-and-metastasis-in-oral-squamous-cell-carcinoma
#17
Hua Zhou, Maricel G Kann, Emily K Mallory, Ying-Hua Yang, Amr Bugshan, Nada O Binmadi, John R Basile
The semaphorins and the plexins are a family of large, cysteine-rich proteins originally identified as regulators of axon growth and lymphocyte activation that are now known to provide motility and positional information for a number of cell and tissue types. For example, our group and others have shown that some malignancies over express Semaphorin 4D (S4D), which acts through its receptor Plexin-B1 (PB1) on endothelial cells to attract blood vessels from the surrounding stroma for the purpose of supporting tumor growth...
December 27, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28033454/enantioselective-disposition-of-r-salmeterol-and-s-salmeterol-in-urine-following-inhaled-dosing-and-application-to-doping-control
#18
Glenn A Jacobson, Morten Hostrup, Christian K Narkowicz, David S Nichols, E Haydn Walters
Salmeterol (USAN, INN, BAN) is a long-acting beta2-adrenoceptor agonist (LABA) widely used in the treatment of airways disease. Although salmeterol is permitted via inhalation by athletes and supratherapeutic dosing may enhance performance, no urine threshold has been established by the World Anti-Doping Agency (WADA). Salmeterol is a chiral compound consisting of (R)- and (S)-enantiomers, normally administered as racemic (rac-) mixture via inhalation. Levels of rac-salmeterol in urine are often below detectable levels and there is surprisingly little information regarding the enantioselectivity of salmeterol pharmacokinetics...
November 7, 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28033109/photoplethysmography-for-an-independent-measure-of-pulsatile-pressure-under-controlled-flow-conditions
#19
Haneen Njoum, Panayiotis A Kyriacou
Noninvasive continuous blood pressure measurements are desirable for patients and clinicians. This work proposes and validates a method for transmural pressure measurement using photoplethysmography (PPG) in an in vitro setup that allows control of pressure and flow conditions. The optimum pulsatile volume measure is obtained by comparing parameters extracted from the photoplethysmographic signal (AC amplitude, normalized pulse volume (NPV) and adjusted pulse volume (APV)). Pulsatile volume can then provide pressure measurements using the exponential pressure-volume (P-V) relationship and validated using the gold standard catheter pressure measurement...
December 29, 2016: Physiological Measurement
https://www.readbyqxmd.com/read/28031525/filamin-c-promotes-lymphatic-invasion-and-lymphatic-metastasis-and-increases-cell-motility-by-regulating-rho-gtpase-in-esophageal-squamous-cell-carcinoma
#20
Kan Tanabe, Yoshinari Shinsato, Tatsuhiko Furukawa, Yoshiaki Kita, Kazuhito Hatanaka, Kentaro Minami, Kohichi Kawahara, Masatatsu Yamamoto, Kenji Baba, Shinichiro Mori, Yasuto Uchikado, Kosei Maemura, Akihide Tanimoto, Shoji Natsugoe
To establish treatments to improve the prognosis of cancer patients, it is necessary to find new targets to control metastasis. We found that expression of FilaminC (FLNC), a member of the actin binding and cross-linking filamin protein family is correlated with lymphatic invasion and lymphatic metastasis in esophageal squamous cell carcinoma (ESCC) by increasing cell motility through activation of Rho GTPase.Immunohistochemistry analysis showed that FLNC expression in ESCC is associated with lymphatic invasion, metastasis, and prognosis...
December 22, 2016: Oncotarget
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