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FEBS Letters

Andreas Schmid, Juliette Sailland, Lisa Novak, Nathalie Baumlin, Nevis Fregien, Matthias Salathe
Wnt signaling is essential for the differentiation of airway epithelial cells during development. Here, we examined the role of Wnt signaling during redifferentiation of ciliated airway epithelial cells in vitro at the air liquid interface (ALI) as a model of airway epithelial repair. Phases of proliferation and differentiation were defined. Markers of squamous metaplasia and epithelial ciliation were followed while enhancing β-catenin signaling by blocking Glycogen Synthase Kinase 3β (GSK3β) with SB216763 and shRNA as well as inhibiting canonical WNT signaling with apical application of Dickkopf 1 (Dkk1)...
September 16, 2017: FEBS Letters
Lorena Tremiño, Alicia Forcada-Nadal, Asunción Contreras, Vicente Rubio
The Synechococcus elongatus COG0325 gene pipY functionally interacts with the nitrogen regulatory gene pipX. As a first step towards a molecular understanding of such interactions, we characterized PipY. This 221-residue protein is monomeric and hosts pyridoxal phosphate (PLP), binding it with limited affinity and losing it upon incubation with D-cycloserine. PipY crystal structures with and without PLP reveal a single-domain monomer folded as the TIM barrel of type III-fold PLP enzymes, with PLP highly exposed, fitting a role for PipY in PLP homeostasis...
September 15, 2017: FEBS Letters
Eckardt Treuter, Rongrong Fan, Zhiqiang Huang, Tomas Jakobsson, Nicolas Venteclef
Macrophage differentiation and signal responses are coordinated by closely linked transcriptional and epigenomic mechanisms that trigger gene expression. In contrast to well-characterized transcriptional activation pathways in response to diverse metabolic and inflammatory signals, we just begin appreciating that transcriptional repression is equally important. Here we will highlight macrophage pathways that are controlled by multifaceted repression events, along with a discussion of underlying regulatory mechanisms and components...
September 13, 2017: FEBS Letters
Carmen S Yong, Daouda Mousatpha Abba Moussa, Gaspard Cretenet, Sandrina Kinet, Valérie Dardalhon, Naomi Taylor
T cells are stimulated by the engagement of antigen, cytokine, pathogen and hormone receptors. While research performed over many years has focused on deciphering the molecular components of these pathways, recent data underscore the importance of the metabolic environment in conditioning responses to receptor engagement. The ability of T cells to undergo a massive proliferation and cytokine secretion in response to receptor signals requires alterations to their bioenergetic homeostasis, allowing them to meet new energetic and biosynthetic demands...
September 13, 2017: FEBS Letters
Himanshu Joshi, Surya Pratap Seniya, Suryanarayanan Venkatesan, Neelam Devidas Patidar, Sanjeev Kumar Singh, Vikas Jain
Most bacteriophages rapidly infect and kill bacteria and, therefore, qualify as the next generation therapeutics for rapidly emerging drug-resistant bacteria such as Mycobacterium tuberculosis. We have previously characterized the mycobacteriophage D29-generated endolysin, Lysin A, for its activity against mycobacteria. Here, we present a detailed characterization of the lysozyme domain (LD) of D29 Lysin A that hydrolyzes peptidoglycan of both Gram-positive and Gram-negative bacteria with high potency. By characterizing an exhaustive LD protein variant library, we have identified critical residues important for LD activity and stability...
September 13, 2017: FEBS Letters
Hairun Pei, Shengnan Han, Shaoyuan Yang, Zhen Lei, Jimin Zheng, Zongchao Jia
The bacterial L9 (bL9) protein expressed and purified from E. coli is stably phosphorylated. We mapped seven Ser/Thr phosphorylation sites, all of which but one are located at the carboxyl-terminal domain (CTD). When a histidine tag is fused to the C-terminus, bL9 is no longer phosphorylated. Phosphorylation of bL9 causes complete disordering of its CTD and helps cell survival under nutrient-limiting conditions. Previous structural studies of the ribosome have shown that bL9 exhibits two distinct conformations, one of which competes with binding of RelA to the 30s rRNA and prevents RelA activation...
September 12, 2017: FEBS Letters
Subashika Govindan, Denis Jabaudon
The adult neocortex is composed of several types of glutamatergic neurons, which are sequentially born from progenitors during development. The extent and nature of progenitor diversity, and how it relates to neuronal diversity, is still poorly understood. In this review, we discuss key features of neocortical progenitors across several species, including their morphological properties, cell-cycling behavior and molecular signatures, and how these features relate to the competence of these cells to generate distinct types of progenies...
September 12, 2017: FEBS Letters
Claudia D Fuchs, Thierry Claudel, Hubert Scharnagl, Tatjana Stojakovic, Michael Trauner
The farnesoid X receptor (FXR) and C/EBP homologous protein (CHOP) have critical functions in hepatic lipid metabolism. Here, we aimed to explore a potential relationship between FXR and CHOP. We fed wild-type (WT) and FXR KO mice a MCD-diet (model of steatohepatitis) and found that Chop mRNA expression is upregulated in WT but not FXR KO mice. Absence of FXR aggravates hepatic inflammation after MCD feeding. In HepG2 cells, we found that Chop expression is regulated in a FXR/Retinoid X receptor (RXR)-dependent manner...
September 12, 2017: FEBS Letters
Clovis S Palmer, Gabriel A Duette, Marc C E Wagner, Darren C Henstridge, Suah Saleh, Candida Pereira, Jingling Zhou, David Simar, Sharon R Lewin, Matias Ostrowski, Joseph M McCune, Suzanne M Crowe
High Glut1 surface expression is associated with increased glycolytic activity in activated CD4+ T cells. PI3K activation measured by p-Akt and OX40 is elevated in CD4+Glut1+ T cells from HIV+ subjects. TCR engagement of CD4+Glut1+ T cells from HIV+ subjects demonstrate hyper-responsive PI3K-mTOR signalling. High basal Glut1 and OX40 on CD4+ T cells from combination antiretroviral therapy (cART)-treated HIV+ patients represent a sufficiently metabolically active state permissive for HIV infection in vitro without external stimuli...
September 11, 2017: FEBS Letters
Shota Hiruma, Tomoko Kamasaki, Kohei Otomo, Tomomi Nemoto, Ryota Uehara
The molecular mechanism that governs cytoskeleton-membrane interaction during animal cytokinesis remains elusive. Here, we investigated the dynamics and functions of ERM (Ezrin/Radixin/Moesin) proteins during cytokinesis in human cultured cells. We found that ezrin is recruited to the cleavage furrow through its membrane-associated domain in a cholesterol-dependent but largely Rho-independent manner. While ERMs are dispensable for furrow ingression, they play a pivotal role in contractile activity of the polar cortex...
September 10, 2017: FEBS Letters
Nikita A Kuldushev, Antonina A Berkut, Steve Peigneur, Jan Tytgat, Eugene V Grishin, Alexander A Vassilevski
Scorpion α-toxins are polypeptides that inhibit voltage-gated sodium channel inactivation. They are divided into mammal, insect and α-like toxins based on their relative activity towards different phyla. Several factors are currently known to influence the selectivity, which are not just particular amino acid residues but also general physical, chemical, and topological properties of toxin structural modules. The objective of this study was to change the selectivity profile of a chosen broadly active α-like toxin, BeM9 from Mesobuthus eupeus, towards mammal-selective...
September 10, 2017: FEBS Letters
Markus Dick, German Erlenkamp, G T T Nguyen, Kerstin Förster, Georg Groth, Holger Gohlke
Phosphoenolpyruvate carboxylase (PEPC) is a key enzyme in the C4 photosynthetic pathway of many of the world's worst weeds and a valuable target to develop C4 plant-selective herbicides. By virtual screening, analog synthesis, and in vitro validation, we identified pyrazolidine-3,5-diones as a new class of small molecules with inhibitory potential down to the submicromolar range against C4 PEPC and a selectivity factor of up to 16 over C3 PEPC. No other biological activity has yet been reported for the best compound, (3-bromophenyl)-4-(3-hydroxybenzylidene)-pyrazolidine-3,5-dione...
September 10, 2017: FEBS Letters
Raphael Ferreira, Francesco Gatto, Jens Nielsen
Bioinformatics tools to design guide-RNAs (gRNAs) in Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems mostly focused on minimizing off-targeting to enhance efficacy of genome editing. However, there are circumstances in which off-targeting might be desirable to target multiple genes simultaneously with a single gRNA. We termed these gRNAs as promiscuous gRNAs. Here, we present a computational workflow to identify promiscuous gRNAs that putatively bind to the region of interest for a defined list of genes in a genome...
September 8, 2017: FEBS Letters
Laura Zanetti-Polzi, Caitlin M Davis, Martin Gruebele, R Brian Dyer, Andrea Amadei, Isabella Daidone
We present a calculation of the amide I' infrared spectra of the folded, unfolded, and intermediate states of the WW domain Fip35, a model system for β-sheet folding. Using an all-atom molecular dy-namics simulation in which multiple folding and unfolding events take place we identify six conformational states and then apply perturbed matrix method quantum-mechanical calculations to determine their amide I' infrared spectra. Our analysis focuses on two states pre-previously identified as Fip35 folding intermediates and suggests that a three-stranded core similar to the folded state core is the main source of the spectroscopic differences between the two intermediates...
September 7, 2017: FEBS Letters
ZhongJi Pu, Fangling Ji, Jingyun Wang, Yue Zhang, Wenhui Sun, Yongming Bao
Meso-2,3-butanediol dehydrogenase catalyzes NAD(+) -dependent conversion of meso-2,3-butanediol to acetoin, a crucial external energy storage molecule in fermentive bacteria. In this study, the active tunnel of meso-2,3- butanediol dehydrogenase was identified. The two short α helixes positioned away from the α4-helix possibly expose the hydrophobic ligand-binding cavity, gating the exit of product and cofactor from the activity pocket. Further MM/GBSA binding free energy analysis shows that Phe212 and Asn146 function as the key product-release sites...
September 5, 2017: FEBS Letters
Jonathan Elegheert, Ann Brigé, Jozef Van Beeumen, Savvas N Savvides
Shewanella oneidensis, a Gram-negative γ-proteobacterium with an extensive redox capacity, possesses four Old Yellow Enzyme (OYE) homologues. Of these, Shewanella Yellow Enzyme 4 (SYE4) is implicated in resistance to oxidative stress. Here, we present a series of high-resolution crystal structures for SYE4 in the oxidized and reduced states, and in complex with phenolic ligands and the nitroaromatic explosive picric acid. The structures unmask new features, including the identification of a binding platform for long-chain hydrophobic molecules...
September 4, 2017: FEBS Letters
Sarah Haßdenteufel, Mark Sicking, Stefan Schorr, Naama Aviram, Claudia Fecher-Trost, Maya Schuldiner, Martin Jung, Richard Zimmermann, Sven Lang
Recently, understanding of protein targeting to the endoplasmic reticulum (ER) was expanded by discovery of multiple pathways that function in parallel to the signal recognition particle (SRP). GET (guided entry of tail-anchored proteins) and SND (SRP independent) are two such targeting pathways described in yeast. So far, no human SND component is functionally characterized. Here, we report hSnd2 as the first constituent of the human SND pathway able to support substrate-specific protein targeting to the ER...
September 1, 2017: FEBS Letters
Aliakbar Khalili Yazdi, Sarita Namjoshi, Jesse Hackett, Nour Ghonaim, Brian H Shilton
We coupled peptides from a CNBr digest of signal-sequenceless maltose binding protein (MBP) to a surface plasmon resonance (SPR) chip. SecA-N95, SecA-N68, and SecA-DM (which consists of only the DEAD Motor domains NBD1 and NBD2) bound to the immobilized peptides; ADP weakened the binding. SecA-DM, which lacks the "preprotein cross-linking domain" (PPXD), displayed the most extensive binding, while an MBP-PPXD chimera showed no binding, demonstrating that the PPXD does not contribute to the binding. We characterized the sequence specificity using oriented peptide libraries; these results enabled synthesis of a 20-residue peptide that was used to recapitulate the results obtained with MBP-derived peptides...
September 1, 2017: FEBS Letters
Mahé Raccaud, David M Suter
During mitosis, gene transcription stops, and the bulk of DNA-binding proteins are excluded from condensed chromosomes. While most gene-specific transcription factors are largely evicted from mitotic chromosomes, a subset remains bound to specific and non-specific DNA sites. Here, we review the current knowledge on the mechanisms leading to the retention of a subset of transcription factors on mitotic chromosomes, and discuss the implications in gene expression regulation and their potential as an epigenetic mechanism controlling stem cell self-renewal and differentiation...
September 1, 2017: FEBS Letters
Miguel Turrero García, Corey Harwell
The ventral telencephalon is the developmental origin of the basal ganglia and the source of neuronal and glial cells that integrate into developing circuits in other areas of the brain. Radial glia in the embryonic subpallium give rise to an enormous diversity of mature cell types, either directly or through other transit-amplifying progenitors. Here, we review current knowledge about these subpallial neural stem cells and their progeny, focusing on the period of neurogenesis. We describe their cell biological features and the extrinsic and intrinsic molecular codes that guide their fate specification in defined temporal and spatial sequences...
September 1, 2017: FEBS Letters
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