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https://www.readbyqxmd.com/read/27907167/infusion-advancing-discovery-of-fusion-genes-and-chimeric-transcripts-from-deep-rna-sequencing-data
#1
Konstantin Okonechnikov, Aki Imai-Matsushima, Lukas Paul, Alexander Seitz, Thomas F Meyer, Fernando Garcia-Alcalde
Analysis of fusion transcripts has become increasingly important due to their link with cancer development. Since high-throughput sequencing approaches survey fusion events exhaustively, several computational methods for the detection of gene fusions from RNA-seq data have been developed. This kind of analysis, however, is complicated by native trans-splicing events, the splicing-induced complexity of the transcriptome and biases and artefacts introduced in experiments and data analysis. There are a number of tools available for the detection of fusions from RNA-seq data; however, certain differences in specificity and sensitivity between commonly used approaches have been found...
2016: PloS One
https://www.readbyqxmd.com/read/27899596/chitars-3-1-the-enhanced-chimeric-transcripts-and-rna-seq-database-matched-with-protein-protein-interactions
#2
Alessandro Gorohovski, Somnath Tagore, Vikrant Palande, Assaf Malka, Dorith Raviv-Shay, Milana Frenkel-Morgenstern
Discovery of chimeric RNAs, which are produced by chromosomal translocations as well as the joining of exons from different genes by trans-splicing, has added a new level of complexity to our study and understanding of the transcriptome. The enhanced ChiTaRS-3.1 database (http://chitars.md.biu.ac.il) is designed to make widely accessible a wealth of mined data on chimeric RNAs, with easy-to-use analytical tools built-in. The database comprises 34 922: chimeric transcripts along with 11 714: cancer breakpoints...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27881666/how-and-why-intralumenal-membrane-fragments-form-during-vacuolar-lysosome-fusion
#3
Sevan Mattie McNally, Erin K Karim, Mahmoud A Vali, Hojatollah Brett, Christopher L Brett
Lysosomal membrane fusion mediates the last step of the autophagy and endocytosis pathways, and supports organelle remodeling and biogenesis. Because fusogenic proteins and lipids concentrate in a ring at the vertex between apposing organelle membranes, the encircled area of membrane can be severed and internalized within the lumen as a fragment upon lipid bilayer fusion. How or why this intralumenal fragment forms during fusion, however, is not entirely clear. To better understand this process, we studied fragment formation during homotypic vacuolar lysosome membrane fusion in Saccharomyces cerevisiae Using cell-free fusion assays and light microscopy, we find that GTPase activation and trans-SNARE complex zippering have opposing effects on fragment formation, and verify that this impacts the morphology of the fusion product and regulates transporter protein degradation...
November 23, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27871970/surgical-management-of-post-traumatic-atlantoaxial-rotatory-fixation-due-to-c2-facet-fracture-5-clinical-cases
#4
H Peyriere, T Graillon, S Pesenti, P Tropiano, B Blondel, S Fuentes
PURPOSE: Report the results of surgical treatment of post-traumatic atlantoaxial rotatory fixation (AARF) due to C2 articular facet fracture in adults. MATERIAL AND METHODS: The records of five patients treated since 2009 for AARF due to a C2 articular facet fracture were analyzed retrospectively. Three women and two men with an average age of 60 years (27-82) were included, one of whom initially had neurological deficits. In all cases, the surgical strategy consisted of posterior fixation: Harms-type in four cases and trans-articular with hooks in one case...
November 18, 2016: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/27856600/tti-621-sirp%C3%AE-fc-a-cd47-blocking-innate-immune-checkpoint-inhibitor-with-broad-anti-tumor-activity-and-minimal-erythrocyte-binding
#5
Penka S Petrova, Natasja N Viller, Mark Wong, Xinli Pang, Gloria H Y Lin, Karen Dodge, Vien Chai, Hui Chen, Vivian Lee, Violetta House, Noel T Vigo, Debbie Jin, Tapfuma Mutukura, Marilyse Charbonneau, Tran Truong, Stéphane Viau, Lisa D Johnson, Emma Linderoth, Eric L Sievers, Saman Maleki Vareki, Rene Figueredo, Macarena Pampillo, James Koropatnick, Suzanne Trudel, Nathan Mbong, Liqing Jin, Jean C Y Wang, Robert A Uger
PURPOSE: The ubiquitously expressed transmembrane glycoprotein CD47 delivers an anti-phagocytic (do-not-eat) signal by binding signal-regulatory protein α (SIRPα) on macrophages. CD47 is over-expressed in cancer cells and its expression is associated with poor clinical outcomes. TTI 621 (SIRPαFc) is a fully human recombinant fusion protein that blocks the CD47:SIRPα-axis by binding to human CD47 and enhancing phagocytosis of malignant cells. Blockade of this inhibitory axis using TTI-621 has emerged as a promising therapeutic strategy to promote tumor cell eradication...
November 17, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27834195/cftr-associated-ligand-cal-is-a-negative-regulator-of-mrp2-expression
#6
Man Li, Carol J Soroka, Kathy Harry, James L Boyer
The multidrug resistance-associated protein 2 (Mrp2) is an ATP-binding cassette transporter that transports a wide variety of organic anions across the apical membrane of epithelial cells. The expression of Mrp2 on the plasma membrane is regulated by protein-protein interactions. CFTR-associated ligand (CAL) interacts with transmembrane proteins via its PDZ domain and reduces their cell surface expression by increasing lysosomal degradation and intracellular retention. Our results showed that CAL is localized at the trans-Golgi network of rat hepatocytes...
November 9, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27802414/solitary-fibrous-tumour-of-the-genitourinary-tract-a-clinicopathological-study-of-11-cases-and-their-association-with-the-nab2-stat6-fusion-gene
#7
Erik Kouba, Novae B Simper, Shaoxiong Chen, Sean R Williamson, David J Grignon, John N Eble, Gregory T MacLennan, Rodolfo Montironi, Antonio Lopez-Beltran, Adeboye O Osunkoya, Shaobo Zhang, Mingsheng Wang, Lisha Wang, Thu Tran, Robert E Emerson, Lee Ann Baldrige, M Francesca Monn, Konstantinos Linos, Liang Cheng
AIMS: To characterise clinicopathological features and clinical outcomes of the genitourinary tract solitary fibrous tumours, incorporating NAB2-STAT6 gene fusion status. METHODS: The presence of the molecular hallmark NAB2-STAT6 gene fusion and for the defining fusion partner product STAT6 was assessed in 11 cases of the genitourinary tract solitary fibrous tumours. NAB2-STAT6 gene fusion analysis was performed using a break-apart fluorescence in situ hybridisation (FISH) probe using a probe cocktail with Bacterial artificial chromosome (BAC) clones for STAT6 and NAB2...
October 31, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27795445/critical-contribution-of-tyr15-in-the-hiv-1-integrase-in-to-facilitate-the-in-assembly-and-non-enzymatic-function-through-the-in-precursor-form-with-reverse-transcriptase
#8
Tatsuro Takahata, Eri Takeda, Minoru Tobiume, Kenzo Tokunaga, Masaru Yokoyama, Yu-Lun Huang, Atsuhiko Hasegawa, Tatsuo Shioda, Hironori Sato, Mari Kannagi, Takao Masuda
: Non-enzymatic roles for HIV-1 integrase (IN) at steps prior to the enzymatic integration step have been reported. To obtain structural and functional insights into the non-enzymatic roles of IN, we performed genetic analyses of HIV-1 IN focusing on a highly conserved Tyr15 in the N-terminal domain (NTD), which has previously been shown to regulate an equilibrium state between two NTD dimer conformations. Substitution of Tyr15 with alanine, histidine, or tryptophan prevented HIV-1 infection and caused severe impairment of reverse transcription without apparent defects in reverse transcriptase (RT) or in capsid disassembly kinetics after entry into cells...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27765817/adaptor-protein-cd2ap-and-l-type-lectin-lman2-regulate-exosome-cargo-protein-trafficking-through-the-golgi-complex
#9
Sang-Ho Kwon, Sekyung Oh, Marisa Nacke, Keith E Mostov, Joshua H Lipschutz
Exosomes, 40-150-nm extracellular vesicles, transport biological macromolecules that mediate intercellular communications. Although exosomes are known to originate from maturation of endosomes into multivesicular endosomes (also known as multivesicular bodies) with subsequent fusion of the multivesicular endosomes with the plasma membrane, it remains unclear how cargos are selected for exosomal release. Using an inducible expression system for the exosome cargo protein GPRC5B and following its trafficking trajectory, we show here that newly synthesized GPRC5B protein accumulates in the Golgi complex prior to its release into exosomes...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27751232/hid-1-is-required-for-homotypic-fusion-of-immature-secretory-granules-during-maturation
#10
Wen Du, Maoge Zhou, Wei Zhao, Dongwan Cheng, Lifen Wang, Jingze Lu, Eli Song, Wei Feng, Yanhong Xue, Pingyong Xu, Tao Xu
Secretory granules, also known as dense core vesicles, are generated at the trans-Golgi network and undergo several maturation steps, including homotypic fusion of immature secretory granules (ISGs), and processing of prehormones to yield active peptides. The molecular mechanisms governing secretory granule maturation are largely unknown. Here, we investigate a highly conserved protein named HID-1 in a mouse model. A conditional knockout of HID-1 in pancreatic β cells leads to glucose intolerance and a remarkable increase in the serum proinsulin/insulin ratio caused by defective proinsulin processing...
October 18, 2016: ELife
https://www.readbyqxmd.com/read/27741567/clathrin-localization-and-dynamics-in-aspergillus-nidulans
#11
Z Schultzhaus, T B Johnson, B D Shaw
Cell growth necessitates extensive membrane remodeling events including vesicle fusion or fission, processes that are regulated by coat proteins. The hyphal cells of filamentous fungi concentrate both exocytosis and endocytosis at the apex. This investigation focuses on clathrin in Aspergillus nidulans, with the aim of understanding its role in membrane remodeling in growing hyphae. We examined clathrin heavy chain (ClaH-GFP) which localized to three distinct subcellular structures: late Golgi (trans-Golgi equivalents of filamentous fungi), which are concentrated just behind the hyphal tip but are intermittently present throughout all hyphal cells; the region of concentrated endocytosis just behind the hyphal apex (the "endocytic collar"); and small, rapidly moving puncta that were seen trafficking long distances in nearly all hyphal compartments...
October 14, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27714612/semisynthesis-of-membrane-attached-proteins-using-split-inteins
#12
Stefanie Hackl, Alanca Schmid, Christian F W Becker
The site-selective installation of lipid modifications on proteins is critically important in our understanding of how membrane association influences the biophysical properties of proteins as well as to study certain proteins in their native environment. Here, we describe the use of split inteins for the C-terminal attachment of lipid-modified peptides to virtually any protein of interest (POI) via protein trans-splicing (PTS). To achieve this, the protein of interest is expressed in fusion with the N-terminal split intein segment and the C-terminal split intein segment is prepared by solid phase peptide synthesis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27714454/plant-specific-4-1-polypeptide-interacts-with-an-endoplasmic-reticulum-protein-related-to-human-bap31
#13
Anna V Pankratenko, Anastasia K Atabekova, Ekaterina A Lazareva, Viktoriia E Baksheeva, Oxana A Zhironkina, Evgeni Yu Zernii, Robert A Owens, Andrey G Solovyev, Sergey Y Morozov
The plant-specific 4/1 protein interacts, both in yeast two-hybrid system and in vitro, and co-localizes in plant cells with plant BAP-like protein, the orthologue of human protein BAP31. In yeast two-hybrid system, we identified a number of Nicotiana benthamiana protein interactors of Nt-4/1, the protein known to affect systemic transport of potato spindle tuber viroid. For one of these interactors, an orthologue of human B-cell receptor-associated protein 31 (BAP31) termed plant BAP-like protein (PBL), the ability to interact with Nt-4/1 was studied in greater detail...
October 6, 2016: Planta
https://www.readbyqxmd.com/read/27708545/chromosomal-abnormality-of-acute-promyelocytic-leukemia-other-than-pml-rara-a-case-report-of-acute-promyelocytic-leukemia-with-del-5q
#14
Osamu Imataki, Makiko Uemura
BACKGROUND: The recent study described a better outcome in acute promyelocytic leukemia patients treated with all-trans retinoic acid and arsenic oxide compared to those treated with all-trans retinoic acid combined with conventional chemotherapy. The pivotal study indicated that favorable-risk acute promyelocytic leukemia patients can be cured without any cytotoxic chemotherapy. Even high-risk patients are treatable with cytotoxic agents. Acute promyelocytic leukemia does not develop only by the dedifferentiation caused by PML-RARA...
2016: BMC Clinical Pathology
https://www.readbyqxmd.com/read/27706038/dimerization-of-the-vacuolar-receptors-atrmr1-and-2-from-arabidopsis-thaliana-contributes-to-their-localization-in-the-trans-golgi-network
#15
Alessandro Occhialini, Guillaume Gouzerh, Gian-Pietro Di Sansebastiano, Jean-Marc Neuhaus
In Arabidopsis thaliana, different types of vacuolar receptors were discovered. The AtVSR (Vacuolar Sorting Receptor) receptors are well known to be involved in the traffic to lytic vacuole (LV), while few evidences demonstrate the involvement of the receptors from AtRMR family (Receptor Membrane RING-H2) in the traffic to the protein storage vacuole (PSV). In this study we focused on the localization of two members of AtRMR family, AtRMR1 and -2, and on the possible interaction between these two receptors in the plant secretory pathway...
September 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27704775/rational-design-of-dual-agonist-antibody-fusions-as-long-acting-therapeutic-hormones
#16
Yan Liu, Ying Wang, Yong Zhang, Tao Liu, Haiqun Jia, Huafei Zou, Qiangwei Fu, Yuhan Zhang, Lucy Lu, Elizabeth Chao, Holly Parker, Van Nguyen-Tran, Weijun Shen, Danling Wang, Peter G Schultz, Feng Wang
Recent studies have suggested that modulation of two or more signaling pathways can achieve substantial weight loss and glycemic stability. We have developed an approach to the generation of bifunctional antibody agonists that activate leptin receptor and GLP-1 receptor. Leptin was fused into the complementarity determining region 3 loop of the light chain alone, or in combination with exendin-4 (EX4) fused at the N-terminus of the heavy chain of Herceptin. The antibody fusions exhibit similar or increased in vitro activities on their cognate receptors, but 50-100-fold longer circulating half-lives in rodents compared to the corresponding native peptides/proteins...
October 5, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27695654/gamete-interactions-require-transmembranous-immunoglobulin-like-proteins-with-conserved-roles-during-evolution
#17
COMMENT
Hitoshi Nishimura, Steven W L'Hernault
C. elegans spe-9 class genes are male germline-enriched in their expression and indispensable during sperm-oocyte fusion. Identification of mammalian orthologs that exhibit similar functions to these C. elegans genes has been a challenge. The mouse Izumo1 gene encodes a sperm-specific, immunoglobulin (Ig)-like transmembrane (TM) protein that is required for gamete fusion. We recently identified the C. elegans spe-45 gene, which shows male germline-enriched expression and encodes an Ig-like TM protein. spe-45 mutant worms produced otherwise normal spermatozoa that cannot fuse with oocytes, causing essentially the same phenotype as that seen in the Izumo1-knockout mice...
2016: Worm
https://www.readbyqxmd.com/read/27683688/comparison-of-alif-vs-xlif-for-l4-5-interbody-fusion-pros-cons-and-literature-review
#18
REVIEW
Mark J Winder, Shanu Gambhir
The incidence of lumbar fusion for the treatment of various degenerative lumbar spine diseases has increased dramatically over the last twenty years. Many lumbar fusion techniques have been developed and popularized, each with its own advantages and disadvantages. Anterior lumbar interbody fusion (ALIF) initially introduced in the 1930's, has become a common and widely accepted technique for lumbar fusions over the last decade offering several advantages over standard posterior lumbar interbody fusion (PLIF) or transforaminal lumbar interbody fusion (TLIF)...
March 2016: Journal of Spine Surgery (Hong Kong)
https://www.readbyqxmd.com/read/27663736/rational-design-of-a-kv1-3-channel-blocking-antibody-as-a-selective-immunosuppressant
#19
Rongsheng E Wang, Ying Wang, Yuhan Zhang, Chase Gabrelow, Yong Zhang, Victor Chi, Qiangwei Fu, Xiaozhou Luo, Danling Wang, Sean Joseph, Kristen Johnson, Arnab K Chatterjee, Timothy M Wright, Vân T B Nguyen-Tran, John Teijaro, Argyrios N Theofilopoulos, Peter G Schultz, Feng Wang
A variable region fusion strategy was used to generate an immunosuppressive antibody based on a novel "stalk-knob" structural motif in the ultralong complementary-determining region (CDR) of a bovine antibody. The potent Kv1.3 channel inhibitory peptides Moka1-toxin and Vm24-toxin were grafted into different CDRs of the humanized antibodies BVK and Synagis (Syn) using both β-sheet and coiled-coil linkers. Structure-activity relationship efforts led to generation of the fusion protein Syn-Vm24-CDR3L, which demonstrated excellent selectivity and potency against effector human memory T cells (subnanomolar to picomolar EC50 values)...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27644261/steric-hindrance-of-snare-transmembrane-domain%C3%A2-organization-impairs-the-hemifusion-to-fusion-transition
#20
Massimo D'Agostino, Herre Jelger Risselada, Andreas Mayer
SNAREs fuse membranes in several steps. Trans-SNARE complexes juxtapose membranes, induce hemifused stalk structures, and open the fusion pore. A recent penetration model of fusion proposed that SNAREs force the hydrophilic C-termini of their transmembrane domains through the hydrophobic core of the membrane(s). In contrast, the indentation model suggests that the C-termini open the pore by locally compressing and deforming the stalk. Here we test these models in the context of yeast vacuole fusion. Addition of small hydrophilic tags renders bilayer penetration by the C-termini energetically unlikely...
September 19, 2016: EMBO Reports
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