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https://www.readbyqxmd.com/read/29136368/split-2-protein-ligation-generates-active-il-6-type-hyper-cytokines-from-inactive-precursors
#1
Jens Mark Moll, Melanie Wehmöller, Nils Christopher Frank, Lisa Homey, Paul Baran, Christoph Garbers, Larissa Lamertz, Jonathan H Axelrod, Eithan Galun, Henning D Mootz, Jürgen Scheller
Trans-signaling of the major pro- and anti-inflammatory cytokines Interleukin (IL)-6 and IL-11 has the unique feature to virtually activate all cells of the body and is critically involved in chronic inflammation and regeneration. Hyper-IL-6 and Hyper-IL-11 are single chain designer trans-signaling cytokines, in which the cytokine and soluble receptor units are trapped in one complex via a flexible peptide linker. Albeit, Hyper-cytokines are essential tools to study trans-signaling in vitro and in vivo, the superior potency of these designer cytokines are accompanied by undesirable stress responses...
November 14, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29131638/lipid-pore-filled-silica-thin-film-membranes-for-biomimetic-recovery-of-dilute-carbohydrates
#2
Shanshan Zhou, Daniel M Schlipf, Emma Caroline Guilfoil, Stephen E Rankin, Barbara Lynn Knutson
Selectively permeable biological membranes containing lipophilic barriers inspire the design of biomimetic carrier-mediated membranes for aqueous solute separation. The recovery of glucose, which can reversibly bind to boronic acid carriers, is examined in lipid pore-filled silica thin film composite membranes with accessible mesopores. The successful incorporation of lipids (1, 2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) and boronic acid carriers ((4-(N-Boc-amino)methyl) phenylboronic acid, BAMP-BA) in the pores of a mesoporous silica (~10 nm pore diameter) through evaporation deposition is verified by confocal microscopy and differential scanning calorimetry (DSC)...
November 13, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29128428/clinical-and-translational-implications-of-ret-rearrangements-in-non-small-cell-lung-cancer
#3
REVIEW
Roberto Ferrara, Nathalie Auger, Edouard Auclin, Benjamin Besse
Since the discovery in 2012 of RET rearrangements in non-small cell lung cancer (NSCLC), at least 12 different fusion variants have been identified, with KIF5B-RET being the most frequent and the best characterized. Unlike ALK and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry, although fluorescence in situ hybridization and reverse transcriptase PCR are fully complementary diagnostic tools. In large retrospective studies, RET rearrangements correlate with adenocarcinoma histology, never-smoking status, younger age, more advanced stage disease, potentially higher chemo-sensitivity (in particular to pemetrexed-based regimens), and coexistence of other genomic alterations...
November 8, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29114056/incremental-heating-of-bishop-tuff-sanidine-reveals-preeruptive-radiogenic-ar-and-rapid-remobilization-from-cold-storage
#4
Nathan L Andersen, Brian R Jicha, Brad S Singer, Wes Hildreth
Accurate and precise ages of large silicic eruptions are critical to calibrating the geologic timescale and gauging the tempo of changes in climate, biologic evolution, and magmatic processes throughout Earth history. The conventional approach to dating these eruptive products using the (40)Ar/(39)Ar method is to fuse dozens of individual feldspar crystals. However, dispersion of fusion dates is common and interpretation is complicated by increasingly precise data obtained via multicollector mass spectrometry...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29113360/microrna-488-inhibits-chemoresistance-of-ovarian-cancer-cells-by-targeting-six1-and-mitochondrial-function
#5
Zhuo Yang, ZiYi Feng, JiaHui Gu, XinHui Li, QianZhe Dong, KuiRan Liu, Yan Li, Ling OuYang
Dysregulation of miR-488 has been implicated in several human cancers. In this study, we aim to explore its expression and biological function in ovarian cancers. We found miR-488 expression was downregulated in ovarian cancer tissues. Using CCK8 and colony formation assay showed that miR-488 inhibited SKOV3 cell proliferation and colony formation, with downregulation of cyclin D1 and cyclin E protein. While miR-488 inhibitor promoted OVCAR3 cell growth and colony formation. Cell viability and Annexin V/PI staining showed that miR-488 downregulated cell survival and increased apoptosis rate when treated with cisplatin and paclitaxel...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113191/how-to-detect-the-rare-bcr-abl-e14a3-transcript-a-case-report-and-literature-review
#6
Lin-Hui Hu, Lian-Fang Pu, Dong-Dong Yang, Cui Zhang, Hui-Ping Wang, Yang-Yang Ding, Man-Man Li, Zhi-Min Zhai, Shudao Xiong
The Philadelphia (Ph; BCR-ABL) chromosome originates from a translocation event between chromosomes 9 and 22, and results in the BCR-ABL fusion gene. In chronic myelogenous leukemia (CML), the BCR-ABL gene is mainly coded for by a major breakpoint cluster region (M-bcr, e13a2 and e14a2). However, in some patients, BCR-ABL genes are encoded by a minor (m)-bcr, e1a2, and a micro (µ)-bcr region, e19a2. These transcripts revealed a different clinical course. The present study described a CML patient whose cytogenetics and FISH analyses of bone marrow revealed a karyotype of 46, XY t(9,22) (q34;q11), while the commercial kits of quantitative PCR (qPCR) failed to detect the BCR-ABL fusion gene...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112376/pressure-induced-melting-of-confined-ice
#7
Kai Sotthewes, Pantelis Bampoulis, Harold J W Zandvliet, Detlef Lohse, Bene Poelsema
The classic regelation experiment of Thomson in the 1850s deals with cutting an ice cube, followed by refreezing. The cutting was attributed to pressure-induced melting but has been challenged continuously, and only lately consensus emerged by understanding that compression shortens the O:H nonbond and lengthens the H-O bond simultaneously. This H-O elongation leads to energy loss and lowers the melting point. The hot debate survived well over 150 years, mainly due to a poorly defined heat exchange with the environment in the experiment...
November 10, 2017: ACS Nano
https://www.readbyqxmd.com/read/29109093/dek-nup214-fusion-identified-by-rna-sequencing-of-an-acute-myeloid-leukemia-with-t-9-12-q34-q15
#8
REVIEW
Ioannis Panagopoulos, Ludmila Gorunova, Synne Torkildsen, Geir E Tjønnfjord, Francesca Micci, Sverre Heim
BACKGROUND/AIM: Given the diagnostic, prognostic, biologic, and even therapeutic impact of leukemia-associated translocations and fusion genes, it is important to detect cryptic genomic rearrangements that may exist in hematological malignancies. CASE REPORT: RNA-sequencing was performed on an acute myeloid leukemia case with the bone marrow karyotype 45,X,-Y,t(9;12) (q34;q15)[16]. RESULTS: The DEK-NUP214 and PRRC2B-DEK fusion genes were found...
November 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29105243/performance-of-multiplex-fusion-gene-testing-in-pediatric-acute-myeloid-leukemia
#9
Yuka Iijima-Yamashita, Hidemasa Matsuo, Miho Yamada, Takao Deguchi, Nobutaka Kiyokawa, Akira Shimada, Akio Tawa, Hiroyuki Takahashi, Daisuke Tomizawa, Takashi Taga, Akitoshi Kinoshita, Souichi Adachi, Keizo Horibe
BACKGROUND: Gene abnormalities, particularly chromosome rearrangements generating gene fusions, are associated with clinical characteristics and prognosis in pediatric acute myeloid leukemia (AML). Karyotyping is generally performed to enable risk stratification; however, the results are not always consistent with those generated by reverse transcription-polymerase chain reaction (RT-PCR), and more accurate and rapid methods are required. METHODS: A total of 487 samples from de novo AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study (n = 448), and acute promyelocytic leukemia (APL) patients enrolled in the JPLSG AML-P05 study (n = 39) were available for this investigation...
November 4, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/29104083/development-and-evaluation-of-a-pan-sarcoma-fusion-gene-detection-assay-using-the-nanostring-ncounter-platform
#10
Kenneth Tou En Chang, Angela Goytain, Tracy Tucker, Aly Karsan, Cheng-Han Lee, Torsten O Nielsen, Tony L Ng
The NanoString nCounter assay is a high-throughput hybridization technique using target-specific probes that can be customized to test for numerous fusion transcripts in a single assay utilizing RNA from formalin-fixed, paraffin-embedded material. We designed a NanoString assay targeting 174 unique fusion junctions in 25 sarcoma types. The study cohort comprised 212 cases, 96 of which showed fusion gene expression by the NanoString assay, including all 20 Ewing sarcomas, 11 synovial sarcomas, and five myxoid liposarcomas tested...
November 2, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29099796/genome-analysis-and-genetic-stability-of-the-cryptophlebia-leucotreta-granulovirus-crlegv-sa-after-15-years-of-commercial-use-as-a-biopesticide
#11
Marcel van der Merwe, Michael D Jukes, Lukasz Rabalski, Caroline Knox, John K Opoku-Debrah, Sean D Moore, Martyna Krejmer-Rabalska, Boguslaw Szewczyk, Martin P Hill
Thaumatotibia leucotreta Meyrick (Lepidoptera: Tortricidae) is an indigenous pest in southern Africa which attacks citrus fruits and other crops. To control T. leucotreta in South Africa, an integrated pest management (IPM) programme incorporating the baculovirus Cryptophlebialeucotreta granulovirus (CrleGV-SA) as a biopesticide has been implemented. This study investigated the genetic stability of a commercially produced CrleGV-SA product that has been applied in the field since 2000. Seven representative full-genome sequences of the CrleGV-SA isolate spanning a 15-year period were generated and compared with one another...
November 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29096381/epitopes-based-drug-design-for-dengue-virus-envelope-protein-a-computational-approach
#12
Abdul Wadood, Aamir Mehmood, Huma Khan, Muhammad Ilyas, Ayaz Ahmad, Mohammed Alarjah, Tareq Abu-Izneid
Dengue virus (DENV) has emerged as a rapidly spreading epidemic throughout the tropical and subtropical regions around the globe. No suitable drug has been designed yet to fight against DENV, therefore, the need for safe and effective antiviral drug has become imperative. The envelope protein of DENV is responsible for mediating the fusion process between viral and host membranes. This work reports an in silico approach to target B and T cell epitopes for dengue envelope protein inhibition. A conserved region "QHGTI" in B and T cell epitopes of dengue envelope glycoprotein was confirmed to be valid for targeting by visualizing its interactions with the host cell membrane TIM-1 protein which acts as a receptor for serotype 2 and 3...
October 20, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29077949/incorporation-of-aptamers-in-the-terminal-loop-of-shrnas-yields-an-effective-and-novel-combinatorial-targeting-strategy
#13
Ka Ming Pang, Daniela Castanotto, Haitang Li, Lisa Scherer, John J Rossi
Gene therapy by engineering patient's own blood cells to confer HIV resistance can potentially lead to a functional cure for AIDS. Toward this goal, we have previously developed an anti-HIV lentivirus vector that deploys a combination of shRNA, ribozyme and RNA decoy. To further improve this therapeutic vector against viral escape, we sought an additional reagent to target HIV integrase. Here, we report the development of a new strategy for selection and expression of aptamer for gene therapy. We developed a SELEX protocol (multi-tag SELEX) for selecting RNA aptamers against proteins with low solubility or stability, such as integrase...
October 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29074139/optogenetic-control-of-focal-adhesion-kinase-signaling
#14
Maximilian Hörner, Claire Chatelle, Wignand W D Mühlhäuser, David R Stocker, Michael Coats, Wilfried Weber, Gerald Radziwill
Focal adhesion kinase (FAK) integrates signaling from integrins, growth factor receptors and mechanical stress to control cell adhesion, motility, survival and proliferation. Here, we developed a single-component, photo-activatable FAK, termed optoFAK, by using blue light-induced oligomerization of cryptochrome 2 (CRY2) to activate FAK-CRY2 fusion proteins. OptoFAK functions uncoupled from physiological stimuli and activates downstream signaling rapidly and reversibly upon blue light exposure. OptoFAK stimulates SRC creating a positive feedback loop on FAK activation, facilitating phosphorylation of paxillin and p130Cas in adherent cells...
October 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29072576/engineering-multifunctional-protein-nanoparticles-by-in-vitro-disassembling-and-reassembling-of-heterologous-building-blocks
#15
Ugutz Unzueta, Naroa Serna, Laura Sánchez-García, Mónica Roldan, Alejandro Sánchez-Chardi, Ramon Mangues, Antonio Villaverde Villaverde, Esther Vázquez
The engineering of protein self-assembling at the nanoscale allows the generation of functional and biocompatible materials, which can be produced by easy biological fabrication. The combination of cationic and histidine-rich stretches in fusion proteins promotes oligomerization as stable protein-only regular nanoparticles that are composed by a moderate number of building blocks. Among other applications, these materials are highly appealing as tools in targeted drug delivery once empowered with peptidic ligands of cell surface receptors...
October 26, 2017: Nanotechnology
https://www.readbyqxmd.com/read/29070682/epistastic-interactions-within-the-jun%C3%A3-n-virus-envelope-glycoprotein-complex-provide-an-evolutionary-barrier-to-reversion-in-the-live-attenuated-candid-1-vaccine
#16
Joanne York, Jack H Nunberg
The Candid#1 strain of Junín virus was developed using a conventional attenuation strategy of serial passage in non-host animals and cultured cells. The live-attenuated Candid#1 vaccine is used in Argentina to protect at-risk individuals against Argentine hemorrhagic fever, but has not been licensed in the United States. Recent studies have revealed that Candid#1 attenuation is entirely dependent on a phenylalanine-to-isoleucine substitution at position 427 in the fusion subunit (GP2) of the viral envelope glycoprotein complex (GPC), thereby raising concerns regarding the potential for reversion to virulence...
October 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29067094/dasatinib-and-chemotherapy-in-a-patient-with-early-t-cell-precursor-acute-lymphoblastic-leukemia-and-nup214-abl1-fusion-a-case-report
#17
Yan Chen, Li Zhang, Jiankun Huang, Xiuli Hong, Jiangning Zhao, Zhao Wang, Kejie Zhang
The present study aimed to evaluate the therapeutic efficacy of dasatinib in a patient with nucleoporin 214-tyrosine protein kinase ABL1 proto-oncogene 1 (NUP214-ABL1)-positive early T-cell precursor-acute lymphoblastic leukemia (ETP-ALL), as well as that of selinexor and dasatinib for NUP214-ABL1-positive ETP-ALL in vitro. ETP leukemia is a form of T-cell ALL (T-ALL) with poor prognosis. The NUP214-ABL1 gene is present in ~6% of T-ALL cases, however the prevalence of NUP214-ABL1 gene expression in ETP-ALL in particular has not yet been verified...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29066631/advancing-a-high-throughput-glycotope-centric-glycomics-workflow-based-on-nanolc-ms-2-product-dependent-ms-3-analysis-of-permethylated-glycans
#18
Cheng-Te Hsiao, Po-Wei Wang, Hua-Chien Chang, Yen-Ying Chen, Shui-Hua Wang, Yijuang Chern, Kay-Hooi Khoo
The intrinsic nature of glycosylation, namely non-template encoded, stepwise elongation and termination with a diverse range of isomeric glyco-epitopes (glycotopes), translates into ambiguity in most cases of mass spectrometry (MS)-based glycomic mapping. It is arguable that whether one needs to delineate every single glycomic entity, which may be counterproductive. Instead, one should focus on identifying as many structural features as possible that would collectively define the glycomic characteristics of a cell or tissue, and how these may change in response to self-programmed development, immuno-activation, and malignant transformation...
October 24, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29056345/a-genetic-tool-to-track-protein-aggregates-and-control-prion-inheritance
#19
Gregory A Newby, Szilvia Kiriakov, Erinc Hallacli, Can Kayatekin, Peter Tsvetkov, Christopher P Mancuso, J Maeve Bonner, William R Hesse, Sohini Chakrabortee, Anita L Manogaran, Susan W Liebman, Susan Lindquist, Ahmad S Khalil
Protein aggregation is a hallmark of many diseases but also underlies a wide range of positive cellular functions. This phenomenon has been difficult to study because of a lack of quantitative and high-throughput cellular tools. Here, we develop a synthetic genetic tool to sense and control protein aggregation. We apply the technology to yeast prions, developing sensors to track their aggregation states and employing prion fusions to encode synthetic memories in yeast cells. Utilizing high-throughput screens, we identify prion-curing mutants and engineer "anti-prion drives" that reverse the non-Mendelian inheritance pattern of prions and eliminate them from yeast populations...
November 2, 2017: Cell
https://www.readbyqxmd.com/read/29053192/dissociation-of-nnos-from-psd-95-promotes-functional-recovery-after-cerebral-ischaemia-in-mice-through-reducing-excessive-tonic-gaba-release-from-reactive-astrocytes
#20
Yu-Hui Lin, Hai-Ying Liang, Ke Xu, Huan-Yu Ni, Jian Dong, Hui Xiao, Lei Chang, Hai-Yin Wu, Fei Li, Dong-Ya Zhu, Chun-Xia Luo
Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein Tat-nNOS-N1-133 or systemic administration of a small molecule ZL006 from days 4 to 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome...
October 20, 2017: Journal of Pathology
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