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https://www.readbyqxmd.com/read/28538724/applying-systems-level-spectral-imaging-and-analysis-to-reveal-the-organelle-interactome
#1
Alex M Valm, Sarah Cohen, Wesley R Legant, Justin Melunis, Uri Hershberg, Eric Wait, Andrew R Cohen, Michael W Davidson, Eric Betzig, Jennifer Lippincott-Schwartz
The organization of the eukaryotic cell into discrete membrane-bound organelles allows for the separation of incompatible biochemical processes, but the activities of these organelles must be coordinated. For example, lipid metabolism is distributed between the endoplasmic reticulum for lipid synthesis, lipid droplets for storage and transport, mitochondria and peroxisomes for β-oxidation, and lysosomes for lipid hydrolysis and recycling. It is increasingly recognized that organelle contacts have a vital role in diverse cellular functions...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#2
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28538683/metabolic-investigations-of-the-molecular-mechanisms-associated-with-parkinson-s-disease
#3
REVIEW
Robert Powers, Shulei Lei, Annadurai Anandhan, Darrell D Marshall, Bradley Worley, Ronald L Cerny, Eric D Dodds, Yuting Huang, Mihalis I Panayiotidis, Aglaia Pappa, Rodrigo Franco
Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar cytoplasmic aggregates of α-synuclein (i.e., Lewy bodies) and the associated loss of dopaminergic cells in the substantia nigra. Mutations in genes such as α-synuclein (SNCA) account for only 10% of PD occurrences. Exposure to environmental toxicants including pesticides and metals (e.g., paraquat (PQ) and manganese (Mn)) is also recognized as an important PD risk factor. Thus, aging, genetic alterations, and environmental factors all contribute to the etiology of PD...
May 24, 2017: Metabolites
https://www.readbyqxmd.com/read/28538170/yap-regulates-actin-dynamics-through-arhgap29-and-promotes-metastasis
#4
Yiting Qiao, Jianxiang Chen, Ying Bena Lim, Megan Louise Finch-Edmondson, Veerabrahma Pratap Seshachalam, Lei Qin, Tingting Jiang, Boon Chuan Low, Himanshu Singh, Chwee Teck Lim, Marius Sudol
Yes-associated protein (YAP) is regulated by mechanical cues via the interaction of the Hippo pathway with cytoskeleton. Previous studies showed that YAP plays a role in regulating the actomyosin network by suppressing Rho GTPase in medaka fish. Here, we identify Rho GTPase activating protein 29 (ARHGAP29) as a transcriptional target of YAP in a human gastric cancer cell line. YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting migration...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538158/glnk-facilitates-the-dynamic-regulation-of-bacterial-nitrogen-assimilation
#5
Adam Gosztolai, Jörg Schumacher, Volker Behrends, Jacob G Bundy, Franziska Heydenreich, Mark H Bennett, Martin Buck, Mauricio Barahona
Ammonium assimilation in Escherichia coli is regulated by two paralogous proteins (GlnB and GlnK), which orchestrate interactions with regulators of gene expression, transport proteins, and metabolic pathways. Yet how they conjointly modulate the activity of glutamine synthetase, the key enzyme for nitrogen assimilation, is poorly understood. We combine experiments and theory to study the dynamic roles of GlnB and GlnK during nitrogen starvation and upshift. We measure time-resolved in vivo concentrations of metabolites, total and posttranslationally modified proteins, and develop a concise biochemical model of GlnB and GlnK that incorporates competition for active and allosteric sites, as well as functional sequestration of GlnK...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28538153/new-continuum-approaches-for-determining-protein-induced-membrane-deformations
#6
David Argudo, Neville P Bethel, Frank V Marcoline, Charles W Wolgemuth, Michael Grabe
The influence of the membrane on transmembrane proteins is central to a number of biological phenomena, notably the gating of stretch activated ion channels. Conversely, membrane proteins can influence the bilayer, leading to the stabilization of particular membrane shapes, topological changes that occur during vesicle fission and fusion, and shape-dependent protein aggregation. Continuum elastic models of the membrane have been widely used to study protein-membrane interactions. These mathematical approaches produce physically interpretable membrane shapes, energy estimates for the cost of deformation, and a snapshot of the equilibrium configuration...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28538152/apoptotic-bax-at-oxidatively-stressed-mitochondrial-membranes-lipid-dynamics-and-permeabilization
#7
Artur Peter Günther Dingeldein, Šárka Pokorná, Martin Lidman, Tobias Sparrman, Radek Šachl, Martin Hof, Gerhard Gröbner
Mitochondria are crucial compartments of eukaryotic cells because they function as the cellular power plant and play a central role in the early stages of programmed cell death (apoptosis). To avoid undesired cell death, this apoptotic pathway is tightly regulated by members of the Bcl-2 protein family, which interact on the external surface of the mitochondria, i.e., the mitochondrial outer membrane (MOM), and modulate its permeability to apoptotic factors, controlling their release into the cytosol. A growing body of evidence suggests that the MOM lipids play active roles in this permeabilization process...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28538143/openrbc-a-fast-simulator-of-red-blood-cells-at%C3%A2-protein-resolution
#8
Yu-Hang Tang, Lu Lu, He Li, Constantinos Evangelinos, Leopold Grinberg, Vipin Sachdeva, George Em Karniadakis
We present OpenRBC, a coarse-grained molecular dynamics code, which is capable of performing an unprecedented in silico experiment-simulating an entire mammal red blood cell lipid bilayer and cytoskeleton as modeled by multiple millions of mesoscopic particles-using a single shared memory commodity workstation. To achieve this, we invented an adaptive spatial-searching algorithm to accelerate the computation of short-range pairwise interactions in an extremely sparse three-dimensional space. The algorithm is based on a Voronoi partitioning of the point cloud of coarse-grained particles, and is continuously updated over the course of the simulation...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28538105/linezolid-induced-lactic-acidosis-the-thin-line-between-bacterial-and-mitochondrial-ribosomes
#9
Alessandro Santini, Dario Ronchi, Manuela Garbellini, Daniela Piga, Alessandro Protti
Introduction - Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid. Areas covered - The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome. Expert opinion - Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes...
May 24, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28537941/pathophysiology-of-anca-associated-vasculitis
#10
Turki Al-Hussain, Maged H Hussein, Walter Conca, Hadeel Al Mana, Mohammed Akhtar
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized as inflammation of small-sized to medium-sized blood vessels and encompasses several clinicopathologic entities including granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited ANCA-associated vasculitis. Over the past several decades, significant progress has been made in understanding the pathophysiology of ANCA-associated vasculitis. Although neutrophils contain a multitude of granular proteins, clinically significant autoantibodies are only recognized against myeloperoxidase and proteinase 3, both of which are present in the azurophilic granules...
May 22, 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28537926/vitamin-d3-induces-vitamin-d-receptor-and-hdac11-binding-to-relieve-the-promoter-of-the-tight-junction-proteins
#11
Feng-Hua Liu, Shan-Shan Li, Xiao-Xi Li, Shuai Wang, Mao-Gang Li, Li Guan, Tian-Gang Luan, Zhi-Gang Liu, Zhan-Ju Liu, Ping-Chang Yang
Intestinal epithelial barrier dysfunction and vitamin D (VitD)-deficiency play a critical role in a large number of diseases. The histone deacetylases (HDAC) are associated with a large number of immune diseases. This study tests a hypothesis that the interaction between VitD and HDAC is associated with the regulation of epithelial barrier functions. In this study, human intestinal epithelial cell line, T84 cells, was cultured into monolayers to be used as a model to test the epithelial barrier functions. We observed that in a VitD-deficient environment, the T84 monolayer barrier function was compromised...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537848/influence-of-endurance-training-on-skeletal-muscle-mitophagy-regulatory-proteins-in-type-2-diabetic-men
#12
Christian Brinkmann, Axel Przyklenk, Alexander Metten, Thorsten Schiffer, Wilhelm Bloch, Klara Brixius, Sebastian Gehlert
BACKGROUND: Mitophagy is a form of autophagy for the elimination of mitochondria. Mitochondrial content and function are reduced in the skeletal muscle of patients with type 2 diabetes mellitus (T2DM). Physical training has been shown to restore mitochondrial capacity in T2DM patients, but the role of mitophagy has not been examined in this context. This study analyzes the impact of a 3-month endurance training on important skeletal muscle mitophagy regulatory proteins and oxidative phosphorylation (OXPHOS) complexes in T2DM patients...
May 24, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28537751/using-neutron-reflectometry-to-characterize-antimicrobial-protein-surface-coatings
#13
Peter W Akers, Andrew J Dingley, Simon Swift, Andrew R J Nelson, Julie Martin, Duncan James McGillivray
Understanding the interaction of adsorbed or covalently immobilized proteins with solid substrates at the molecular level guides the successful design of functionalized surfaces used in biomedical applications. In this report, neutron reflectometry (NR) was used to characterize the structure of surface-attached antimicrobial protein films, with antimicrobial activity assessed using an adaption of the Japanese Industrial Standard Test JIS Z 2801. NR allowed parameters influencing bioactivity to be measured at nanometer resolution and for conclusions about structural characteristics relating to bioactivity to be drawn...
May 24, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28537725/the-color-of-cation-%C3%AF-interactions-subtleties-of-amine-tryptophan-interaction-energetics-allow-for-radical-like-visible-absorbance-and-fluorescence
#14
Laura J Juszczak, Azaria S Eisenberg
Several peptides and a protein with an inter- or intramolecular cation-π interaction between tryptophan (Trp) and an amine cation are shown to absorb and fluoresce in the visible region of the spectrum. Titration of indole with sodium hydroxide or ammonium hydroxide yields an increasing visible fluorescence as well. Visible absorption and multi-peaked fluorescence excitation spectra correlate with experimental absorption spectra and the vibrational modes of calculated absorption spectra for the neutral Trp radical...
May 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28535664/characterization-of-alphax-i-domain-binding-to-receptors-for-advanced-glycation-end-products-rage
#15
Dolgorsuren Buyannemekh, Sang-Uk Nham
The b2 integrins are cell surface transmembrane proteins regulating leukocyte functions, such as adhesion and migration. Two members of b2 integrin, aMb2 and aXb2, share the leukocyte distribution profile and integrin aXb2 is involved in antigen presentation in dendritic cells and transendothelial migration of monocytes and macrophages to atherosclerotic lesions. Receptor for advanced glycation end products (RAGE), a member of cell adhesion molecules, plays an important role in chronic inflammation and atherosclerosis...
May 24, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28535649/-cancer-associated-fibroblasts-regulate-the-chemoresistance-of-lung-cancer-cell-line-a549-via-sdf-1-secretion
#16
F Zou, Z H Zhang, Y T Zhang, J Q Zhao, X L Zhang, C L Wen, X Y Song, W M Zhou
Objective: To investigate whether cancer-associated- fibroblasts (CAF), the key component of tumor microenvironment, regulate the chemoresistant capacity of lung cancer cell line A549 through SDF-1 secretion. Methods: Primary cell isolation techniques was used to isolate cancer-associated-fibroblasts from lung cancer patients. MTT assay was applied to determine the proliferation and chemoresistance of A549 cells. Quantative PCR was used to detect the mRNA changes of Bcl-xL. Western blotting was used to detect the protein expression of Bcl-xL...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28535648/-effect-of-%C3%AE-40p53-isoform-on-enhancing-the-pro-apoptotic-function-of-p53-in-tumor-cells
#17
B S Wang, H W Zhao, L X Qiao, J Q Shan, Q S Hou, D X Chen, H L Guo
Objective: To investigate the effect of Δ40p53, an alternative spliced isoform of p53 lacking the N-ter minus, on the pro-apoptotic function of p53. Methods: The wild-type p53 was ectopically expressed in HCT116-p53(-/-) (endogenous Δ40p53 expression), HCT116-p53(+ /+) (wild-type p53) and H1299 (p53-null) cells by adenoviral delivery, while Δ40p53 plasmid were transfected into these cells to overexpress Δ40p53. The levels of Δ40p53 and p53 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative PCR...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28535647/-effects-of-overexpression-of-mir-17-92-gene-cluster-on-the-biological-characteristics-of-prostate-cancer-cells-and-its-mechanism
#18
P Zhou, L Ma, J Zhou, J J Xu, F Liu, F Guo
Objective: To explore the effect and mechanism of over-expression of miR-17-92 gene cluster on the biological characteristics of prostate cancer cells. Methods: DU145 cells were transfected with miR-17-92 gene expression plasmid and clones with stable ectopic miR-17-92 overexpression were established. The cell viabilities of DU145-17-92 and DU145-control cells were monitored by xCELLigence system. Cell proliferation and apoptosis were analyzed by Ki-67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28535377/mechanism-of-ska-recruitment-by-ndc80-complexes-to-kinetochores
#19
Paweł Ł Janczyk, Katarzyna A Skorupka, John G Tooley, Daniel R Matson, Cortney A Kestner, Thomas West, Owen Pornillos, P Todd Stukenberg
Yeast use the ring-shaped Dam1 complex to slide down depolymerizing microtubules to move chromosomes, but current models suggest that other eukaryotes do not have a sliding ring. We visualized Ndc80 and Ska complexes on microtubules by electron microscopic tomography to identify the structure of the human kinetochore-microtubule attachment. Ndc80 recruits the Ska complex so that the V shape of the Ska dimer interacts along protofilaments. We identify a mutant of the Ndc80 tail that is deficient in Ska recruitment to kinetochores and in orienting Ska along protofilaments in vitro...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28535347/preparation-and-characterization-of-protein-loaded-electrospun-fiber-mat-and-its-release-kinetics
#20
Peng Wen, Yan Wen, Xiao Huang, Minhua Zong, Hong Wu
For the enhancement of protein's bioavailability, a specific delivery system was developed by coaxial electrospinning. Bovine serum albumin (BSA) was used as protein model and the core-sheath fiber mat was fabricated using sodium alginate as shell layer and the BSA-loaded chitosan nanoparticle that prepared previously as core layer. By optimizing electrospinning parameters, uniform fibers with diameters ranging from 200 nm to 600 nm were obtained, and transmission electron microscopy and confocal laser scanning microscopy revealed its core-sheath structure...
May 23, 2017: Journal of Agricultural and Food Chemistry
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