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https://www.readbyqxmd.com/read/28107443/identification-of-the-pla2g6-c-1579g-a-missense-mutation-in-papillon-dog-neuroaxonal-dystrophy-using-whole-exome-sequencing-analysis
#1
Masaya Tsuboi, Manabu Watanabe, Kazumi Nibe, Natsuko Yoshimi, Akihisa Kato, Masahiro Sakaguchi, Osamu Yamato, Miyuu Tanaka, Mitsuru Kuwamura, Kazuya Kushida, Takashi Ishikura, Tomoyuki Harada, James Kenn Chambers, Sumio Sugano, Kazuyuki Uchida, Hiroyuki Nakayama
Whole exome sequencing (WES) has become a common tool for identifying genetic causes of human inherited disorders, and it has also recently been applied to canine genome research. We conducted WES analysis of neuroaxonal dystrophy (NAD), a neurodegenerative disease that sporadically occurs worldwide in Papillon dogs. The disease is considered an autosomal recessive monogenic disease, which is histopathologically characterized by severe axonal swelling, known as "spheroids," throughout the nervous system. By sequencing all eleven DNA samples from one NAD-affected Papillon dog and her parents, two unrelated NAD-affected Papillon dogs, and six unaffected control Papillon dogs, we identified 10 candidate mutations...
2017: PloS One
https://www.readbyqxmd.com/read/28107182/the-nitrobenzoxadiazole-derivative-mc3181-blocks-melanoma-invasion-and-metastasis
#2
Anastasia De Luca, Debora Carpanese, Maria Cristina Rapanotti, Tara Mayte Suarez Viguria, Maria Antonietta Forgione, Dante Rotili, Chiara Fulci, Egidio Iorio, Luigi Quintieri, Sergio Chimenti, Luca Bianchi, Antonio Rosato, Anna Maria Caccuri
The novel nitrobenzoxadiazole (NBD) derivative MC3181 is endowed with remarkable therapeutic activity in mice bearing both sensitive and vemurafenib-resistant human melanoma xenografts. Here, we report that subtoxic concentrations of this compound significantly reduced invasiveness of BRAF-V600D mutated WM115 and WM266.4 melanoma cell lines derived from the primary lesion and related skin metastasis of the same patient, respectively. The strong antimetastatic activity of MC3181 was observed in both 2D monolayer cultures and 3D multicellular tumor spheroids, and confirmed in vivo by the significant decrease in the number of B16-F10 melanoma lung metastases in drug-treated mice...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28105152/evaluation-by-quantitative-image-analysis-of-anticancer-drug-activity-on-multicellular-spheroids-grown-in-3d-matrices
#3
Aurélie Gomes, Adrien Russo, Guillaume Vidal, Elise Demange, Pauline Pannetier, Zied Souguir, Jean-Michel Lagarde, Bernard Ducommun, Valérie Lobjois
Pharmacological evaluation of anticancer drugs using 3D in vitro models provides invaluable information for predicting in vivo activity. Artificial matrices are currently available that scale up and increase the power of such 3D models. The aim of the present study was to propose an efficient and robust imaging and analysis pipeline to assess with quantitative parameters the efficacy of a particular cytotoxic drug. HCT116 colorectal adenocarcinoma tumor cell multispheres were grown in a 3D physiological hyaluronic acid matrix...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28096447/pbp1b-glycosyltransferase-and-transpeptidase-activities-play-different-essential-roles-during-the-de-novo-regeneration-of-rod-shaped-morphology-in-escherichia-coli
#4
Dev K Ranjit, Matthew A Jorgenson, Kevin D Young
: Peptidoglycan is a vital component of nearly all cell wall-bearing bacteria and is a valuable target for antibacterial therapy. However, despite decades of work, there remain important gaps in understanding how this macromolecule is synthesized and molded into a three-dimensional structure that imparts specific morphologies to individual cells. Here, we investigate the particularly enigmatic area of how peptidoglycan is synthesized and shaped during the first stages of creating cell shape de novo, that is, in the absence of a pre-existing template...
January 17, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28093366/strategy-for-constructing-vascularized-adipose-units-in-poly-l-glutamic-acid-hydrogel-porous-scaffold-through-inducing-in-situ-formation-of-ascs-spheroids
#5
Kunxi Zhang, Li Song, Jia Wang, Shifeng Yan, Guifei Li, Lei Cui, Jingbo Yin
: Vascularization is of great importance to adipose tissue regeneration. Here we introduced a paradigm that using scaffold to induce ASC spheroids, so to promote vascularized adipose tissue regeneration. Poly (L-glutamic acid) (PLGA) was activated by EDC, followed by being cross-linked by Adipic dihydrazide (ADH) to form a homogeneous hydrogel. Lyophilization was then carried out to create porous structure. The PLGA hydrogel scaffold possessed a significant swollen hydrophilic network to weaken cell-scaffold adhesion but drive ASCs to aggregate to form spheroids...
January 13, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28091986/shift-of-microrna-profile-upon-glioma-cell-migration-using-patient-derived-spheroids-and-serum-free-conditions
#6
Sune Munthe, Bo Halle, Henning B Boldt, Helle Christiansen, Steffen Schmidt, Vivek Kaimal, Jessica Xu, Sonya Zabludoff, Jan Mollenhauer, Frantz R Poulsen, Bjarne W Kristensen
Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery. Another major reason is tumor cells having a so-called cancer stem cell phenotype being therefore resistant towards traditional chemo- and radiotherapy. A group of novel molecular targets are microRNAs (miRNAs). MiRNAs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. The aim of this study was to identify differentially expressed miRNAs in migrating GBM cells using serum-free stem cell conditions...
January 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28090777/biodegradable-neuro-compatible-peptide-hydrogel-promotes-neurite-outgrowth-shows-significant-neuroprotection-and-delivers-anti-alzheimer-drug
#7
Anindyasundar Adak, Gaurav Das, Surajit Barman, Saswat Mohapatra, Debmalya Bhunia, Batakrishna Jana, Surajit Ghosh
A novel neuro-compatible peptide based hydrogel has been designed and developed, which contains microtubule stabilizing and neuroprotective short peptide. This hydrogel shows strong three dimensional cross-linked fibrillary networks, which can capture water molecules. Interestingly, this hydrogel serves as excellent biocompatible soft-material for 2D and 3D (neuro-sphere) neuron cell culture and provides stability of key cytoskeleton filaments such as microtubule and actin. Remarkably, it was observed that this hydrogel slowly enzymatically degrades and releases neuroprotective peptide, which promotes neurite outgrowth of neuron cell as well as exhibits excellent neuroprotection against anti-NGF induced toxicity in neuron cells...
January 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28090668/studies-of-anticancer-drug-cytotoxicity-based-on-long-term-hepg2-spheroid-culture-in-a-microfluidic-system
#8
Agnieszka Zuchowska, Karina Kwapiszewska, Michal Chudy, Artur Dybko, Zbigniew Brzozka
Cell-on-a-chip systems have become promising devices to study the effectiveness of new anticancer drugs recently. Several microdevices for liver cancer culture and evaluation of the drug cytotoxicity have been reported. However, there are still no proven reports about high-throughput and simple methods for the evaluation of drug cytotoxicity on liver cancer cells. The paper presents the results of the effects of the anticancer drug (5-fluorouracil, 5-FU) on the HepG2 spheroids as a model of liver cancer. The experiments were based on the long-term 3D spheroid culture in the microfluidic system and monitoring of the effect of 5-FU at two selected concentrations (0...
January 16, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28089786/3-carboxyphenylboronic-acid-modified-carboxymethyl-chitosan-nanoparticles-for-improved-tumor-targeting-and-inhibitory
#9
Xin Wang, Bing Wei, Xu Cheng, Jun Wang, Rupei Tang
Carboxymethyl chitosan-based nanoparticles (CM NPs) were prepared, and were further modified with a tumor-homing ligand (3-carboxyphenylboronic acid, 3-CPBA) to give tumor-targeting nanoparticles (CB NPs). Particle sizes were measured by dynamic light scattering, while the morphology was observed via transmission electron microscopy and scanning electronic microscope. The results show that CM and CB NPs are spherical-like, and kinetically stable in various conditions. Doxorubicin (DOX) as a model drug was successfully encapsulated to give CM-DOX and CB-DOX NPs...
January 12, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28089542/parallelization-and-high-performance-computing-enables-automated-statistical-inference-of-multi-scale-models
#10
Nick Jagiella, Dennis Rickert, Fabian J Theis, Jan Hasenauer
Mechanistic understanding of multi-scale biological processes, such as cell proliferation in a changing biological tissue, is readily facilitated by computational models. While tools exist to construct and simulate multi-scale models, the statistical inference of the unknown model parameters remains an open problem. Here, we present and benchmark a parallel approximate Bayesian computation sequential Monte Carlo (pABC SMC) algorithm, tailored for high-performance computing clusters. pABC SMC is fully automated and returns reliable parameter estimates and confidence intervals...
January 10, 2017: Cell Systems
https://www.readbyqxmd.com/read/28089517/hypoxia-induces-a-hif-1-dependent-transition-from-collective-to-amoeboid-dissemination-in-epithelial-cancer-cells
#11
Steffi Lehmann, Veronika Te Boekhorst, Julia Odenthal, Roberta Bianchi, Sjoerd van Helvert, Kristian Ikenberg, Olga Ilina, Szymon Stoma, Jael Xandry, Liying Jiang, Reidar Grenman, Markus Rudin, Peter Friedl
Cancer metastases arise from a multi-step process that requires metastasizing tumor cells to adapt to signaling input from varying tissue environments [1]. As an early metastatic event, cancer cell dissemination occurs through different migration programs, including multicellular, collective, and single-cell mesenchymal or amoeboid migration [2-4]. Migration modes can interconvert based on changes in cell adhesion, cytoskeletal mechanotransduction [5], and/or proteolysis [6], most likely under the control of transcriptional programs such as the epithelial-to-mesenchymal transition (EMT) [7, 8]...
January 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28087483/cell-number-per-spheroid-and-electrical-conductivity-of-nanowires-influence-the-function-of-silicon-nanowired-human-cardiac-spheroids
#12
Yu Tan, Dylan Richards, Robert C Coyle, Jenny Yao, Ruoyu Xu, Wenyu Gou, Hongjun Wang, Donald R Menick, Bozhi Tian, Ying Mei
: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide an unlimited cell source to treat cardiovascular diseases, the leading cause of death worldwide. However, current hiPSC-CMs retain an immature phenotype that leads to difficulties for integration with adult myocardium after transplantation. To address this, we recently utilized electrically conductive silicon nanowires (e-SiNWs) to facilitate self-assembly of hiPSC-CMs to form nanowired hiPSC cardiac spheroids...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28077488/id2-controls-specification-of-lgr5-intestinal-stem-cell-progenitors-during-gut-development
#13
Lira Nigmatullina, Maxim Norkin, Margarita M Dzama, Berith Messner, Sergi Sayols, Natalia Soshnikova
The adult intestinal stem cells (ISCs), their hierarchies, mechanisms of maintenance and differentiation have been extensively studied. However, when and how ISCs are established during embryogenesis remains unknown. We show here that the transcription regulator Id2 controls the specification of embryonic Lgr5(+) progenitors in the developing murine small intestine. Cell fate mapping analysis revealed that Lgr5(+) progenitors emerge at E13.5 in wild-type embryos and differ from the rest on the intestinal epithelium by a characteristic ISC signature...
January 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28076843/pax-5-is-a-potent-regulator-of-e-cadherin-and-breast-cancer-malignant-processes
#14
Sami Benzina, Annie-Pier Beauregard, Roxann Guerrette, Stéphanie Jean, Mame Daro Faye, Mark Laflamme, Emmanuel Maïcas, Nicolas Crapoulet, Rodney J Ouellette, Gilles A Robichaud
Pax-5, an essential transcription factor for B lymphocyte development, has been linked with the development and progression of lymphoid cancers and carcinoma. In contrast to B-cell cancer lesions, the specific expression signatures and roles of Pax-5 in breast cancer progression are relatively unknown. In the present study, we set out to profile Pax-5 expression in mammary tissues and elucidate the cellular and molecular roles of Pax-5 in breast cancer processes. Using immunohistology on mammary tissue arrays, Pax-5 was detected in a total of 298/306 (97...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075531/three-dimensional-imaging-flow-cytometry-through-light-sheet-fluorescence-microscopy
#15
REVIEW
Emilio J Gualda, Hugo Pereira, Gabriel G Martins, Rui Gardner, Nuno Moreno
Flow cytometry is the tool of choice for high-speed acquisition and analysis of large cell populations, with the tradeoff of lacking intracellular spatial information. Although in the last decades flow cytometry systems that can actually acquire two-dimensional spatial information were developed, some of the limitations remained though, namely constrains related to sample size and lack of depth or dynamic information. The combination of fluidics and light-sheet illumination has the potential to address these limitations...
January 11, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28075401/anti-neuroblastoma-properties-of-a-recombinant-sunflower-lectin
#16
Marcela Pinedo, Melanie Genoula, María Ximena Silveyra, André De Oliveira Carvalho, Mariana Regente, Marianela Del Río, Júlia Ribeiro Soares, Valdirene Moreira Gomes, Laura De La Canal
According to their sugar recognition specificity, plant lectins are proposed as bioactive proteins with potential in cancer treatment and diagnosis. Helja is a mannose-specific jacalin-like lectin from sunflower which was shown to inhibit the growth of certain fungi. Here, we report its recombinant expression in a prokaryotic system and its activity in neurobalstoma cells. Helja coding sequence was fused to the pET-32 EK/LIC, the enterokinase/Ligation-independent cloning vector and a 35 kDa protein was obtained in Escherichia coli representing Helja coupled to thioredoxin (Trx)...
January 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28074628/s100a4-metastasin-positive-mesenchymal-canine-mammary-tumour-spheroids-reduce-tenascin-c-synthesis-under-dmso-exposure-in-vitro
#17
S Kau, I Miller, A Tichy, C Gabriel
In breast cancer research S100A4-positive tumour-associated stromal cells are assumed as primary source of Tenascin C (TNC) in the metastatic environment. Aim of the present study was to isolate and characterize S100A4/TNC positive stromal canine mammary tumour (CMT) cells. Cells grown as scaffold-free spheroids were investigated for S100A4, TNC, and proliferative activity under 1.8% DMSO stimulation by means of Western blot and immunohistochemistry. DMSO is a commonly used drug solvent despite well-known side effects on cells including TNC expression...
January 11, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28069506/one-step-fabrication-of-hydrogel-microcapsules-with-hollow-core-for-assembly-and-cultivation-of-hepatocyte-spheroids
#18
Christian Siltanen, Michaela Diakataou, Jeremy Lowen, Amranul Haque, Ali Rahimian, Gulnaz Stybayeva, Alexander Revzin
: 3D hepatic microtissues can serve as valuable liver analogues for cell-based therapies and for hepatotoxicity screening during preclinical drug development. However, hepatocytes rapidly dedifferentiate in vitro, and typically require 3D cultures systems or co-cultures for phenotype rescue. In this work we present a novel microencapsulation strategy, utilizing coaxial flow-focusing droplet microfluidics to fabricate microcapsules with liquid core and poly(ethylene glycol) (PEG) shell...
January 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28069038/motility-of-glioblastoma-cells-is-driven-by-netrin-1-induced-gain-of-stemness
#19
Irene Ylivinkka, Harri Sihto, Olli Tynninen, Yizhou Hu, Aki Laakso, Riku Kivisaari, Pirjo Laakkonen, Jorma Keski-Oja, Marko Hyytiäinen
BACKGROUND: Glioblastoma is an untreatable brain cancer. The tumors contain a population of stem-like cells which are highly invasive and resistant to therapies. These cells are the main reason for the lethality of glioblastoma. Extracellular guidance molecule netrin-1 promotes the invasiveness and survival of various cancer cell types. We have previously found that netrin-1 activates Notch signaling, and Notch signaling associates with cell stemness. Therefore, we have here investigated the effects of netrin-1 on glioblastoma pathogenesis and glioblastoma cell stemness...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28068060/structural-and-functional-basis-of-c-methylation-of-coumarin-scaffolds-by-novo
#20
Joanna C Sadler, Chun-Wa Chung, Julie E Mosley, Glenn A Burley, Luke D Humphreys
C-methylation of aromatic small molecules by C-methyltransferases (C-MTs) is an important biological trans-formation that involves C-C bond formation using S-adenosyl-L-methionine (SAM) as the methyl donor. Here, two advanc-es in the mechanistic understanding of C-methylation of the 8-position of coumarin substrates catalyzed by the C-MT No-vO from Streptomyces Spheroides are described. First, a crystal structure of NovO reveals the Arg116-Asn117 and His120-Arg121 motifs are essential for coumarin substrate binding...
January 9, 2017: ACS Chemical Biology
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