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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/28538669/the-peroxisome-mitochondria-connection-how-and-why
#4
REVIEW
Marc Fransen, Celien Lismont, Paul Walton
Over the past decades, peroxisomes have emerged as key regulators in overall cellular lipid and reactive oxygen species metabolism. In mammals, these organelles have also been recognized as important hubs in redox-, lipid-, inflammatory-, and innate immune-signaling networks. To exert these activities, peroxisomes must interact both functionally and physically with other cell organelles. This review provides a comprehensive look of what is currently known about the interconnectivity between peroxisomes and mitochondria within mammalian cells...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538572/intratendinous-injection-of-hydrogel-for-reseeding-decellularized-human-flexor-tendons
#5
Chao Long, Michael G Galvez, Anais Legrand, Lydia-Marie Joubert, Zhen Wang, Arhana Chattopadhyay, James Chang, Paige M Fox
BACKGROUND: Decellularized cadaveric tendons are a potential source for reconstruction. Reseeding to enhance healing is ideal; however, cells placed on the tendon surface result in inadequate delivery. The authors used an injection technique to evaluate intratendinous cell delivery. METHODS: Decellularized tendons were reseeded with adipose-derived stem cells in culture, and injected with fetal bovine serum or hydrogel. PKH26-stained cells in cross-section were quantified...
June 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28538179/hand2-target-gene-regulatory-networks-control-atrioventricular-canal-and-cardiac-valve-development
#6
Frédéric Laurent, Ausra Girdziusaite, Julie Gamart, Iros Barozzi, Marco Osterwalder, Jennifer A Akiyama, Joy Lincoln, Javier Lopez-Rios, Axel Visel, Aimée Zuniga, Rolf Zeller
The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538175/extracellular-vesicles-from-a-helminth-parasite-suppress-macrophage-activation-and-constitute-an-effective-vaccine-for-protective-immunity
#7
Gillian Coakley, Jana L McCaskill, Jessica G Borger, Fabio Simbari, Elaine Robertson, Marissa Millar, Yvonne Harcus, Henry J McSorley, Rick M Maizels, Amy H Buck
Recent studies have demonstrated that many parasites release extracellular vesicles (EVs), yet little is known about the specific interactions of EVs with immune cells or their functions during infection. We show that EVs secreted by the gastrointestinal nematode Heligmosomoides polygyrus are internalized by macrophages and modulate their activation. EV internalization causes downregulation of type 1 and type 2 immune-response-associated molecules (IL-6 and TNF, and Ym1 and RELMα) and inhibits expression of the IL-33 receptor subunit ST2...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538172/using-hescs-to-probe-the-interaction-of-the-diabetes-associated-genes-cdkal1-and-mt1e
#8
Min Guo, Tuo Zhang, Xue Dong, Jenny Zhaoying Xiang, Minxiang Lei, Todd Evans, Johannes Graumann, Shuibing Chen
Genome-wide association studies (GWASs) have identified many disease-associated variant alleles, but understanding whether and how different genes/loci interact requires a platform for probing how the variant alleles act mechanistically. Isogenic mutant human embryonic stem cells (hESCs) provide an unlimited resource to derive and study human disease-relevant cells. Here, we focused on CDKAL1, linked by GWASs to diabetes. Through transcript profiling, we find that expression of the metallothionein (MT) gene family, also linked by GWASs to diabetes, is significantly downregulated in CDKAL1(-/-) cells that have been differentiated to insulin-expressing pancreatic beta-like cells...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538170/yap-regulates-actin-dynamics-through-arhgap29-and-promotes-metastasis
#9
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/28538152/apoptotic-bax-at-oxidatively-stressed-mitochondrial-membranes-lipid-dynamics-and-permeabilization
#10
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
#11
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/28538101/chemical-endgroup-modified-diblock-copolymers-elucidate-anchor-and-chain-mechanism-of-membrane-stabilization
#12
Evelyne M Houang, Karen J Haman, Mihee Kim, Wenjia Zhang, Dawn A Lowe, Yuk Yin Sham, Timothy P Lodge, Benjamin J Hackel, Frank S Bates, Joseph M Metzger
Block copolymers can be synthesized in an array of architectures and compositions to yield diverse chemical properties. The triblock copolymer Poloxamer 188 (P188), the family archetype, consisting of a hydrophobic polypropylene oxide core flanked by hydrophilic polyethylene oxide chains, can stabilize cellular membranes during stress. However, little is known regarding the molecular basis of membrane interaction by copolymers in living organisms. By leveraging diblock architectural design, discrete end-group chemistry modifications can be tested...
May 24, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28538085/circulating-heparan-sulfate-fragments-attenuate-histone-induced-lung-injury-independently-of-histone-binding
#13
Yanlin Zhang, Sarah M Haeger, Yimu Yang, Kyrie L Dailey, Joshay A Ford, Eric P Schmidt
Extracellular histones are cationic damage-associated molecular pattern molecules capable of directly inducing cellular injury via charge-mediated interactions with plasma membranes. Accordingly, histones released into the plasma during critical illness are known to contribute to the onset and propagation of lung injury. Vascular injury (with consequent degradation of the endothelial glycocalyx) simultaneously releases anionic heparan sulfate fragments (hexa- to octasaccharides in size) into the plasma. It is unknown whether this endogenous release of heparan sulfate fragments modulates charge-dependent histone cytotoxicity, or if exogenous heparan sulfate fragments could therapeutically attenuate histone-induced lung injury...
May 23, 2017: Shock
https://www.readbyqxmd.com/read/28537941/pathophysiology-of-anca-associated-vasculitis
#14
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
#15
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/28537913/interaction-of-microrna-21-145-and-smad3-domain-specific-phosphorylation-in-hepatocellular-carcinoma
#16
Ji Yu Wang, Meng Fang, Alex Boye, Chao Wu, Jia Jun Wu, Ying Ma, Shu Hou, Yue Kan, Yan Yang
MicroRNAs 21 and 145 exhibit inverse expression in Hepatocellular carcinoma (HCC), but how they relate to Smad3 C-terminal and Link region phosphorylation (pSmad3C and pSmad3L) downstream of TGF-β/MAPK signaling, remains inconclusive. Our results suggest microRNA-145 targets Smad3 in HepG2 cells. Decreased tumor volume and increased apoptosis were produced in both microRNA-21 antagomir and microRNA-145 agomir groups compared to controls. Inhibition of TβRI and MAPK (ERK, JNK, and p38) activation respectively produced decreased microRNA-21 but increased microRNA-145 expression...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537895/interaction-of-glycosphingolipids-gd3-and-gd2-with-growth-factor-receptors-maintains-breast-cancer-stem-cell-phenotype
#17
Yuh-Jin Liang, Chen-Yu Wang, I-An Wang, Yi-Wen Chen, Li-Tzu Li, Chuang-Yu Lin, Ming-Yi Ho, Tsung-Lung Chou, Ya-Hui Wang, Shih-Pin Chiou, Yu-Ju Lin, John Yu
Many studies have suggested that disialogangliosides, GD2 and GD3, are involved in the development of various tumor types. However, the functional relationships between ganglioside expression and cancer development or aggressiveness are not fully described. GD3 is upregulated in approximately half of all invasive ductal breast carcinoma cases, and enhanced expression of GD3 synthase (GD3S, alpha-N-acetylneuraminide alpha-2,8-sialyltransferase) in estrogen receptor-negative breast tumors, was shown to correlate with reduced overall patient survival...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537728/antimalarial-inhibitors-targeting-serine-hydroxymethyltransferase-shmt-with-in-vivo-efficacy-and-analysis-of-their-binding-mode-based-on-x-ray-cocrystal-structures
#18
Geoffrey Schwertz, Matthias C Witschel, Matthias Rottmann, Roger Bonnert, Ubolsree Leartsakulpanich, Penchit Chitnumsub, Aritsara Jaruwat, Wanwipa Ittarat, Anja Schäfer, Raphael A Aponte, Susan A Charman, Karen L White, Abhijit Kundu, Surajit Sadhukhan, Mel Lloyd, Gail M Freiberg, Myron Srikumaran, Marc Siggel, Adrian Zwyssig, Pimchai Chaiyen, François Diederich
Target-based approaches towards new antimalarial treatments are highly valuable to prevent resistance development. We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3...
May 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28535664/characterization-of-alphax-i-domain-binding-to-receptors-for-advanced-glycation-end-products-rage
#19
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
#20
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]
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