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https://www.readbyqxmd.com/read/29161261/mrna-processing-in-mutant-zebrafish-lines-generated-by-chemical-and-crispr-mediated-mutagenesis-produces-unexpected-transcripts-that-escape-nonsense-mediated-decay
#1
Jennifer L Anderson, Timothy S Mulligan, Meng-Chieh Shen, Hui Wang, Catherine M Scahill, Frederick J Tan, Shao J Du, Elisabeth M Busch-Nentwich, Steven A Farber
As model organism-based research shifts from forward to reverse genetics approaches, largely due to the ease of genome editing technology, a low frequency of abnormal phenotypes is being observed in lines with mutations predicted to lead to deleterious effects on the encoded protein. In zebrafish, this low frequency is in part explained by compensation by genes of redundant or similar function, often resulting from the additional round of teleost-specific whole genome duplication within vertebrates. Here we offer additional explanations for the low frequency of mutant phenotypes...
November 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29159923/sea-trout-adapt-their-migratory-behaviour-in-response-to-high-salmon-lice-concentrations
#2
E Halttunen, K-Ø Gjelland, S Hamel, R-M Serra-Llinares, R Nilsen, P Arechavala-Lopez, J Skarðhamar, I A Johnsen, L Asplin, Ø Karlsen, P-A Bjørn, B Finstad
Sea trout face growth-mortality trade-offs when entering the sea to feed. Salmon lice epizootics resulting from aquaculture have shifted these trade-offs, as salmon lice might both increase mortality and reduce growth of sea trout. We studied mortality and behavioural adaptations of wild sea trout in a large-scale experiment with acoustic telemetry in an aquaculture intensive area that was fallowed (emptied of fish) synchronically biannually, creating large variations in salmon lice concentrations. We tagged 310 wild sea trout during 3 years, and gave half of the individuals a prophylaxis against further salmon lice infestation...
November 21, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29159606/preoperative-68-ga-dota-somatostatin-analog-pet-ct-hybrid-imaging-increases-detection-rate-of-intra-abdominal-small-intestinal-neuroendocrine-tumor-lesions
#3
Olov Norlén, Harald Montan, Per Hellman, Peter Stålberg, Anders Sundin
BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are the most common form of neoplasm in the small bowel. Radiological identification of primary tumors (PT), which may be multiple, is difficult, and therefore palpation of the entire small bowel is routinely performed during laparotomy. The aim was to determine detection rates of PT and peritoneal carcinomatosis (PC) with (68)Ga-DOTATOC/TATE-PET/CT in comparison with i.v. contrast-enhanced computed tomography (CE-CT) and thus to clarify whether modern functional imaging can mitigate the need for palpation of bowel during surgery enabling oncologically adequate laparoscopic resection...
November 20, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/29159155/how-to-escape-stentriever-wedging-in-an-open-cell-carotid-stent-during-mechanical-thrombectomy-for-tandem-cervical-internal-carotid-artery-and-middle-cerebral-artery-occlusion
#4
Hae Won Rho, Won Ki Yoon, Jang Hun Kim, Jong Hyun Kim, Taek Hyun Kwon
We present 2 cases of complicated mechanical thrombectomy involving tandem cervical internal carotid artery and middle cerebral artery occlusion using the Solitaire FR stent and simultaneous carotid stent angioplasty. During the procedures, the Solitaire stents containing the thrombus were wedged into the open-cell carotid stents, which were already deployed for proximal flow restoration. We describe the methods used to avoid and overcome such complications.
September 2017: Journal of Cerebrovascular and Endovascular Neurosurgery
https://www.readbyqxmd.com/read/29158816/dual-targeting-theranostic-system-with-mimicking-apoptosis-to-promote-myocardial-infarction-repair-via-modulation-of-macrophages
#5
Jingli Chen, Jun Yang, Ruiyuan Liu, Chenmeng Qiao, Zhiguo Lu, Yuanjie Shi, Zhanming Fan, Zhenzhong Zhang, Xin Zhang
Currently unsatisfactory treatment of myocardial infarction (MI) is due to the unbridled inflammation and the delayed diagnosis at the early stage. To address these problems, firstly, phosphatidylserine (PS) was used to modulate the phenotypes of macrophages (MΦ) and resolve the early inflammation via binding to PS receptors (PSR) on macrophage surface. Secondly, highly-sensitive magnetic iron oxide nanocubes (MIONs) were adopted to realize the early visualization via magnetic resonance imaging (MRI). However, the major drawback for MIONs as contrast agents was their hydrophobic properties and insufficient delivery...
2017: Theranostics
https://www.readbyqxmd.com/read/29158788/programmed-death-ligand-1-pd-l1-expression-in-primary-angiosarcoma
#6
Gerardo Botti, Giosuè Scognamiglio, Laura Marra, Antonio Pizzolorusso, Maurizio Di Bonito, Rossella De Cecio, Monica Cantile, Annarosaria De Chiara
Angiosarcomas are rare malignant endothelial-cell tumors of vascular or lymphatic origin, and are among the most aggressive subtypes of soft-tissue sarcomas. The prognosis is poor and treatment is challenging in many cases. PD-1/PD-L1 pathway plays a critical role in immune escape of tumor cells. Recent studies described that PD-L1 is widely expressed in various types of cancer, providing the basis for the development of PD1/PD-L1 antibodies as anti-cancer immunotherapy. Despite the well-known potential of PD-L1 as prognostic and predictive biomarker, only few studies described its IHC expression in cancer subtypes for the extreme difficulty in developing standard protocol with the different antibody clones available...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158381/superhydrophobic-diving-flies-ephydra-hians-and-the-hypersaline-waters-of-mono-lake
#7
Floris van Breugel, Michael H Dickinson
The remarkable alkali fly, Ephydra hians, deliberately crawls into the alkaline waters of Mono Lake to feed and lay eggs. These diving flies are protected by an air bubble that forms around their superhydrophobic cuticle upon entering the lake. To study the physical mechanisms underlying this process we measured the work required for flies to enter and leave various aqueous solutions. Our measurements show that it is more difficult for the flies to escape from Mono Lake water than from fresh water, due to the high concentration of Na2CO3 which causes water to penetrate and thus wet their setose cuticle...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29158269/the-glucocorticoid-receptor-is-a-key-player-for-prostate-cancer-cell-survival-and-a-target-for-improved-anti-androgen-therapy
#8
Martin Puhr, Julia Hoefer, Andrea Eigentler, Christian Ploner, Florian Handle, Georg Schaefer, Jan Kroon, Angela Leo, Isabel M Heidegger, Iris E Eder, Zoran Culig, Gabri van der Pluijm, Helmut Klocker
PURPOSE: The major obstacle in the management of advanced prostate cancer (PCa) is the occurrence of resistance to endocrine-therapy. Although the androgen receptor (AR) has been linked to therapy failure, the underlying escape mechanisms have not been fully clarified. Being closely related to the AR, the glucocorticoid receptor (GR) has been suggested to play a role in enzalutamide and docetaxel resistance. Given that glucocorticoids are frequently applied to PCa patients, it is essential to unravel the exact role of the GR in PCa progression...
November 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29157281/identification-of-immunogenic-proteins-of-the-cysticercoid-of-hymenolepis-diminuta
#9
Anna Sulima, Justyna Bień, Kirsi Savijoki, Anu Näreaho, Rusłan Sałamatin, David Bruce Conn, Daniel Młocicki
BACKGROUND: A wide range of molecules are used by tapeworm metacestodes to establish successful infection in the hostile environment of the host. Reports indicating the proteins in the cestode-host interactions are limited predominantly to taeniids, with no previous data available for non-taeniid species. A non-taeniid, Hymenolepis diminuta, represents one of the most important model species in cestode biology and exhibits an exceptional developmental plasticity in its life-cycle, which involves two phylogenetically distant hosts, arthropod and vertebrate...
November 21, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29157014/construction-and-cellular-uptake-evaluation-of-redox-responsitive-docetaxel-prodrug-self-assembled-nanoparticles
#10
Guolian Ren, Pei Chen, Jiaqi Tang, Rongrong Wang, Shuai Duan, Ruili Wang, Yin Xie, Shuqiu Zhang
Docetaxel (DTX) solution has some serious adverse side effects. A redox-responsitive DTX prodrug synthesized in our laboratory was used to prepare DTX prodrug self-assembled nanoparticles (DSNPs) with the method of nanoprecipitation. This study aimed to optimize the formulation to develop stable preparation for the delivery of DTX. Single-factor test was used to evaluate the effects of the preparation concentration of DTX prodrug, stirring speed, the types of stabilizers and temperature on the prescription process of DSNPs...
November 21, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29156694/pdac-derived-exosomes-enrich-the-microenvironment-in-mdscs-in-a-smad4-dependent-manner-through-a-new-calcium-related-axis
#11
Daniela Basso, Elisa Gnatta, Andrea Padoan, Paola Fogar, Sara Furlanello, Ada Aita, Dania Bozzato, Carlo-Federico Zambon, Giorgio Arrigoni, Chiara Frasson, Cinzia Franchin, Stefania Moz, Thomas Brefort, Thomas Laufer, Filippo Navaglia, Sergio Pedrazzoli, Giuseppe Basso, Mario Plebani
Tumor genetics and escape from immune surveillance concur in the poor prognosis of PDAC. In this study an experimental model was set up to verify whether SMAD4, deleted in about 55% PDAC and associated with poor prognosis, is involved in determining immunosuppression through Exosomes (Exo). Potential mechanisms and mediators underlying SMAD4-dependent immunosuppression were evaluated by studying intracellular calcium (Fluo-4), Exo-miRNAs (microarray) and Exo-proteins (SILAC). Two PDAC cell lines expressing (BxPC3-SMAD4+) or not-expressing (BxPC3) SMAD4 were used to prepare Exo-enriched conditioned media, employed in experiments with blood donors PBMCs...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156677/overcoming-resistance-to-single-agent-therapy-for-oncogenic-braf-gene-fusions-via-combinatorial-targeting-of-mapk-and-pi3k-mtor-signaling-pathways
#12
Payal Jain, Amanda Silva, Harry J Han, Shih-Shan Lang, Yuankun Zhu, Katie Boucher, Tiffany E Smith, Aesha Vakil, Patrick Diviney, Namrata Choudhari, Pichai Raman, Christine M Busch, Tim Delaney, Xiaodong Yang, Aleksandra K Olow, Sabine Mueller, Daphne Haas-Kogan, Elizabeth Fox, Phillip B Storm, Adam C Resnick, Angela J Waanders
Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156346/abcg2-mediated-suppression-of-chlorin-e6-accumulation-and-photodynamic-therapy-efficiency-in-glioblastoma-cell-lines-can-be-reversed-by-ko143
#13
Sara A Abdel Gaber, Patricia Müller, Wolfgang Zimmermann, Dirk Hüttenberger, Rainer Wittig, Mahmoud H Abdel Kader, Herbert Stepp
BACKGROUND: Photodynamic therapy (PDT) of malignant brain tumors is a promising adjunct to standard treatment, especially if tumor stem cells thought to be responsible for tumor progression and therapy resistance were also susceptible to this kind of treatment. However, some photosensitizers have been reported to be substrates of ABCG2, one of the membrane transporters mediating resistance to chemotherapy. Here we investigate, whether inhibition of ABCG2 can restore sensitivity to photosensitizer chlorin e6-mediated PDT...
October 28, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29156227/low-physiological-arousal-and-high-impulsivity-as-predictors-of-self-injurious-thoughts-and-behaviors-among-adolescents
#14
Jaclyn T Aldrich, Madeline D Wielgus, Amy H Mezulis
Self-injurious thoughts and behaviors are used to escape or regulate aversive physiological states during stress. Low sympathetic nervous system arousal during stress has been shown to confer risk. This risk may be exacerbated by trait impulsivity; adolescents high in impulsivity are more likely to rashly use maladaptive regulation strategies. We examined this relationship longitudinally in a sample of adolescents ages 10 to 14 (55.4% female) from the United States. Consistent with our hypothesis, low arousal during stress and high trait impulsivity interacted to predict the use of self-injurious thoughts and behaviors over a six-month period...
November 17, 2017: Journal of Adolescence
https://www.readbyqxmd.com/read/29156096/males-that-drop-a-sexually-selected-weapon-grow-larger-testes
#15
Paul N Joseph, Zachary Emberts, Daniel A Sasson, Christine W Miller
Costly sexually selected weapons are predicted to trade off with postcopulatory traits, such as testes. Although weapons can be important for achieving access to females, individuals of some species can permanently drop (i.e. autotomize) their weapons, without regeneration, to escape danger. We capitalized on this natural behavior to experimentally address whether the loss of a sexually selected weapon leads to increased testes investment in the leaf-footed cactus bug, Narnia femorata Stål (Hemiptera: Coreidae)...
November 20, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/29155844/hypoxia-and-hypoxia-inducible-factor-hif-downregulate-antigen-presenting-mhc-class-i-molecules-limiting-tumor-cell-recognition-by-t-cells
#16
Shalini Sethumadhavan, Murillo Silva, Phaethon Philbrook, Thao Nguyen, Stephen M Hatfield, Akio Ohta, Michail V Sitkovsky
Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF...
2017: PloS One
https://www.readbyqxmd.com/read/29155762/high-throughput-analysis-of-locomotor-behavior-in-the-drosophila-island-assay
#17
Ilse Eidhof, Michaela Fenckova, Dei M Elurbe, Bart van de Warrenburg, Anna Castells Nobau, Annette Schenck
Advances in next-generation sequencing technologies contribute to the identification of (candidate) disease genes for movement disorders and other neurological diseases at an increasing speed. However, little is known about the molecular mechanisms that underlie these disorders. The genetic, molecular, and behavioral toolbox of Drosophila melanogaster makes this model organism particularly useful to characterize new disease genes and mechanisms in a high-throughput manner. Nevertheless, high-throughput screens require efficient and reliable assays that, ideally, are cost-effective and allow for the automatized quantification of traits relevant to these disorders...
November 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155516/association-of-il-12bpro-polymorphism-with-tumor-infiltrating-dendritic-cells-in-colorectal-cancer
#18
Elina Aleksandrova, Tatyana Vlaykova, Julian Ananiev, Maya Gulubova
PURPOSE: Chronic inflammation is a key component in the development and progression of colorectal cancer (CRC). A notable hallmark of the inflammation process is the release of pro-inflammatory cytokines by infiltrating cells of the immune system. Defects in dendritic cells (DCs) recruitment, maturation and cytokine release are a hallmark of the CRC strategy to escape immune surveillance.The purpose of our study was to evaluate the possible role of IL-12B polymorphism in the promoter region of the IL-12B gene (rs17860508) as a genetic factor contributing to the risk for CRC development...
July 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29155460/antarctic-emerald-rockcod-have-the-capacity-to-compensate-for-warming-when-uncoupled-from-co2-acidification
#19
Brittany E Davis, Erin E Flynn, Nathan A Miller, Frederick A Nelson, Nann A Fangue, Anne E Todgham
Increases in atmospheric CO2 levels and associated ocean changes are expected to have dramatic impacts on marine ecosystems. Although the Southern Ocean is experiencing some of the fastest rates of change, few studies have explored how Antarctic fishes may be affected by co-occurring ocean changes, and even fewer have examined early life stages. To date, no studies have characterized potential trade-offs in physiology and behavior in response to projected multiple climate change stressors (ocean acidification and warming) on Antarctic fishes...
November 20, 2017: Global Change Biology
https://www.readbyqxmd.com/read/29155453/large-scale-bleaching-of-corals-on-the-great-barrier-reef
#20
T P Hughes, J T Kerry, T Simpson
In 2015-2016, record temperatures triggered a pan-tropical episode of coral bleaching. In the southern hemisphere summer of March-April 2016, we used aerial surveys to measure the level of bleaching on 1,156 individual reefs throughout the 2,300 km length of the Great Barrier Reef, the world's largest coral reef system. The accuracy of the aerial scores was ground-truthed with detailed underwater surveys of bleaching at 260 sites (104 reefs), allowing us to compare aerial and underwater bleaching data with satellite-derived temperatures and with associated model predictions of bleaching...
November 20, 2017: Ecology
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