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Sho Kurihara, Masato Fujioka, Tomohiko Yoshida, Makoto Koizumi, Kaoru Ogawa, Hiromi Kojima, Hirotaka James Okano
Hearing research has long been facilitated by rodent models, although in some diseases, human symptoms cannot be recapitulated. The common marmoset (Callithrix jacchus) is a small, easy-to-handle New World monkey which has a similar anatomy of the temporal bone, including the middle ear ossicular chains and inner ear to humans, than in comparison with that of rodents. Here, we report a reproducible, safe, and rational surgical approach to the cochlear round window niche for the drug delivery to the inner ear of the common marmoset...
February 27, 2018: Journal of Visualized Experiments: JoVE
Yuta Kasagi, Prasanna M Chandramouleeswaran, Kelly A Whelan, Koji Tanaka, Veronique Giroux, Medha Sharma, Joshua Wang, Alain J Benitez, Maureen DeMarshall, John W Tobias, Kathryn E Hamilton, Gary W Falk, Jonathan M Spergel, Andres J Klein-Szanto, Anil K Rustgi, Amanda B Muir, Hiroshi Nakagawa
Background & Aims: Aberrations in the esophageal proliferation-differentiation gradient are histologic hallmarks in eosinophilic esophagitis (EoE) and gastroesophageal reflux disease. A reliable protocol to grow 3-dimensional (3D) esophageal organoids is needed to study esophageal epithelial homeostasis under physiological and pathologic conditions. Methods: We modified keratinocyte-serum free medium to grow 3D organoids from endoscopic esophageal biopsies, immortalized human esophageal epithelial cells, and murine esophagi...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Geoffrey S Meltzner, James T Heaton, Yunbin Deng, Gianluca De Luca, Serge H Roy, Joshua C Kline
Each year thousands of individuals require surgical removal of their larynx (voice box) due to trauma or disease, and thereby require an alternative voice source or assistive device to verbally communicate. Although natural voice is lost after laryngectomy, most muscles controlling speech articulation remain intact. Surface electromyographic (sEMG) activity of speech musculature can be recorded from the neck and face, and used for automatic speech recognition to provide speech-to-text or synthesized speech as an alternative means of communication...
December 2017: IEEE/ACM Transactions on Audio, Speech, and Language Processing
Samuel Ortega, Himar Fabelo, Rafael Camacho, María de la Luz Plaza, Gustavo M Callicó, Roberto Sarmiento
Hyperspectral imaging (HSI) is an emerging technology for medical diagnosis. This research work presents a proof-of-concept on the use of HSI data to automatically detect human brain tumor tissue in pathological slides. The samples, consisting of hyperspectral cubes collected from 400 nm to 1000 nm, were acquired from ten different patients diagnosed with high-grade glioma. Based on the diagnosis provided by pathologists, a spectral library of normal and tumor tissues was created and processed using three different supervised classification algorithms...
February 1, 2018: Biomedical Optics Express
Andrew S Fister, Lena Landherr, Siela N Maximova, Mark J Guiltinan
Theobroma cacao , the source of cocoa, suffers significant losses to a variety of pathogens resulting in reduced incomes for millions of farmers in developing countries. Development of disease resistant cacao varieties is an essential strategy to combat this threat, but is limited by sources of genetic resistance and the slow generation time of this tropical tree crop. In this study, we present the first application of genome editing technology in cacao, using Agrobacterium-mediated transient transformation to introduce CRISPR/Cas9 components into cacao leaves and cotyledon cells...
2018: Frontiers in Plant Science
Concetta Saponaro, Sara Sergio, Antonio Coluccia, Maria De Luca, Giuseppe La Regina, Luca Mologni, Valeria Famiglini, Valentina Naccarato, Daniela Bonetti, Candice Gautier, Stefano Gianni, Daniele Vergara, Michel Salzet, Isabelle Fournier, Cecilia Bucci, Romano Silvestri, Carlo Gambacorti Passerini, Michele Maffia, Addolorata Maria Luce Coluccia
Nuclear activated β-catenin plays a causative role in colorectal cancers (CRC) but remains an elusive therapeutic target. Using human CRC cells harboring different Wnt/β-catenin pathway mutations in APC/KRAS or β-catenin/KRAS genes, and both genetic and pharmacological knockdown approaches, we show that oncogenic β-catenin signaling negatively regulates the expression of NHERF1 (Na+ /H+ exchanger 3 regulating factor 1), a PDZ-adaptor protein that is usually lost or downregulated in early dysplastic adenomas to exacerbate nuclear β-catenin activity...
March 19, 2018: Oncogene
Mikhail M Savitski, Nico Zinn, Maria Faelth-Savitski, Daniel Poeckel, Stephan Gade, Isabelle Becher, Marcel Muelbaier, Anne J Wagner, Katrin Strohmer, Thilo Werner, Stephanie Melchert, Massimo Petretich, Anna Rutkowska, Johanna Vappiani, Holger Franken, Michael Steidel, Gavain M Sweetman, Omer Gilan, Enid Y N Lam, Mark A Dawson, Rab K Prinjha, Paola Grandi, Giovanna Bergamini, Marcus Bantscheff
Protein degradation plays important roles in biological processes and is tightly regulated. Further, targeted proteolysis is an emerging research tool and therapeutic strategy. However, proteome-wide technologies to investigate the causes and consequences of protein degradation in biological systems are lacking. We developed "multiplexed proteome dynamics profiling" (mPDP), a mass-spectrometry-based approach combining dynamic-SILAC labeling with isobaric mass tagging for multiplexed analysis of protein degradation and synthesis...
March 3, 2018: Cell
M Chand, D S Keller, H M Joshi, L Devoto, M Rodriguez-Justo, R Cohen
BACKGROUND: In colon cancer, appropriate tumour excision and associated lymphadenectomy directly impact recurrence and survival outcomes. Currently, there is no standard for mesenteric lymphadenectomy, with a lymph node yield of 12 acting as a surrogate quality marker. Our goal was to determine the safety and feasibility of indocyanine green (ICG) fluorescence imaging to demonstrate lymphatic drainage in colon cancer in a dose-escalation study. METHODS: A prospective pilot study of colon cancer patients undergoing curative laparoscopic resection was performed...
March 17, 2018: Techniques in Coloproctology
John R Best, Janice J Eng, Jennifer C Davis, Robin Hsiung, Peter A Hall, Laura E Middleton, Peter Graf, Charles H Goldsmith, Teresa Liu-Ambrose
INTRODUCTION: Cerebrovascular disease-such as stroke-is the second most common cause of dementia (ie, vascular dementia). Specifically, a stroke increases one's risk for dementia by a factor of two. Thus, stroke survivors represent a target population in need of intervention strategies to promote cognitive function and prevent dementia. The current standard of care in stroke rehabilitation does not adequately address the significant cognitive consequences of stroke, especially for those who are in the chronic phase (ie, >12 months since an index stroke)...
March 17, 2018: BMJ Open
Buyun Chen, Pingping Lu, Dugan Freeman, Yang Gao, Edna Choo, Kevin DeMent, Scott Savage, Kelly Zhang, Dennis Milanwoski, Lichuan Liu, Brian Dean, Yuzhong Deng
The pH labile metabolite, hydrophobicity, high oral dose and systematic exposure of GDC-0810 posed tremendous challenges to develop a LC-MS method for a stable isotope labeled aBA study. In this study, we explored practical solutions to balance stability and sensitivity and to cope with the impact of high Cp.o. to Ci.v. ratio on the labeling selection and assay dynamic range. A [13 C9 ] GDC-0810 was synthesized to minimize the isotopic interference between PO dose, internal standard and I.V. microtracer. A highly sensitive LC-MS assay was validated for quantitation of [13 C9 ] GDC-0810 from 5 to 1250 pg/mL...
February 23, 2018: Journal of Pharmaceutical and Biomedical Analysis
Reinaldo Uribe-San-Martín, Ethel Ciampi, Roberta Di Giacomo, Macarena Vásquez, Claudia Cárcamo, Jaime Godoy, Giorgio Lo Russo, Laura Tassi
OBJECTIVE: Our aim in this retrospective study was to explore whether corpus callosum atrophy could predict the post-surgical seizure control in patients with temporal lobe epilepsy associated with Hippocampal Sclerosis (HS). METHODS: We used the Corpus Callosum Index (CCI) obtained from best mid-sagittal T2/FLAIR or T1-weighted MRI at two time-points, more than one year apart. CCI has been mainly used in Multiple Sclerosis (MS), but not in epilepsy, so we tested the validity of our results performing a proof of concept cohort, incorporating MS patients with and without epilepsy...
March 3, 2018: Epilepsy Research
Alfonso Blázquez-Castro, Lucas L Colombo, Silvia I Vanzulli, Juan C Stockert
The photothermal effect is one of the most promising photonic procedures currently under development to successfully treat several clinical disorders, none the least some kinds of cancer. At present, this field is undergoing a renewed interest due to advances in both photothermal materials and better-suited light sources. However, scientific studies in this area are sometimes hampered by the relative unavailability of state-of-art materials or the complexity of setting up a dedicated optical facility. Here, we present a simple and affordable approach to do research in the photothermal field that relies on a commercial NIR laser pointer and a readily available everyday pigment: China ink...
March 16, 2018: Lasers in Medical Science
Sebastian Kress, Johannes Baur, Christoph Otto, Natalie Burkard, Joris Braspenning, Heike Walles, Joachim Nickel, Marco Metzger
In tissue engineering, the generation and functional maintenance of dense voluminous tissues is mainly restricted due to insufficient nutrient supply. Larger three-dimensional constructs, which exceed the nutrient diffusion limit become necrotic and/or apoptotic in long-term culture if not provided with an appropriate vascularization. Here, we established protocols for the generation of a pre-vascularized biological scaffold with intact arterio-venous capillary loops from rat intestine, which is decellularized under preservation of the feeding and draining vascular tree...
March 16, 2018: Scientific Reports
Guo-Qiang Zhang, Guangming Xing, Licong Cui
One of the basic challenges in developing structural methods for systematic audition on the quality of biomedical ontologies is the computational cost usually involved in exhaustive sub-graph analysis. We introduce ANT-LCA, a new algorithm for computing all non-trivial lowest common ancestors (LCA) of each pair of concepts in the hierarchical graph induced by an ontology. The computation of LCA is a fundamental step for non-lattice approach for ontology quality assurance. Distinct from existing approaches, ANT-LCA only computes LCAs for non-trivial pairs, those having at least one common ancestor...
March 13, 2018: Journal of Biomedical Informatics
Maria J Gonzalez-Moa, Bieke Van Dorst, Ole Lagatie, Ann Verheyen, Lieven Stuyver, Marco A Biamonte
Three O. volvulus immunogenic peptide sequences recently discovered by peptide microarray were adapted to a lateral flow assay (LFA). The LFA employs gold nanoshells as novel high-contrast reporter nanoparticles and detects a serological response against the 3 peptides, found in OvOC9384, OvOC198, and OvOC5528, respectively. When tested on 118 sera from O. volvulus infected patients and 208 control sera, the LFA was 90, 63, and 98% sensitive for each peptide, respectively, and 99-100% specific vs. samples from healthy volunteers...
March 16, 2018: ACS Infectious Diseases
Maria Siemionow, Joanna Cwykiel, Ahlke Heydemann, Jesus Garcia, Enza Marchese, Krzysztof Siemionow, Erzsebet Szilagyi
Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD...
March 15, 2018: Stem Cell Reviews
S T Ayrton, X Chen, R M Bain, C J Pulliam, M Achmatowicz, T G Flick, D Ren, R G Cooks
Proof of concept evidence is presented for a new method for the determination of isoaspartate, an important post-translational modification. Chemical derivatization is performed using common reagents for the modification of carboxylic acids and shown to yield suitable diagnostic information with regard to isomerization at the aspartate residue. The diagnostic gas phase chemistry is probed by collision-induced dissociation mass spectrometry, on the timescale of the MS experiment and semi-quantitative calibration of the percentage of isoaspartate in a peptide sample is demonstrated...
March 15, 2018: Journal of the American Society for Mass Spectrometry
Beibei Zhang, Qiao Wang, Xinhui Xu, Qiang Xia, Feifei Long, Weiwei Li, Yingchun Shui, Xinyi Xia, Jinke Wang
This study develops a new method for detecting target DNA based on Cas9 nuclease, which was named as CARP, representing CRISPR- or Cas9/sgRNAs-associated reverse PCR. This technique detects target DNA in three steps: (1) cleaving the detected DNA sample with Cas9 in complex with a pair of sgRNAs specific to target DNA; (2) ligating the cleaved DNA with DNA ligase; (3) amplifying target DNA with PCR. In the ligation step, the Cas9-cut target DNA was ligated into intramolecular circular or intermolecular concatenated linear DNA...
March 15, 2018: Analytical and Bioanalytical Chemistry
Evangelos G Papanikolaou, Hakan Yarali, Evi Timotheou, Michael Grynberg, Odysseas Zafeiratis, Herman Tournaye, Robert Najdecki
Introduction: A drawback of gonadotropin-releasing hormone (GnRH) antagonist protocols in in vitro fertilization (IVF) is that they have limited flexibility in cycle programming. This proof of concept study explored the efficacy of a single-dose, long-acting GnRH antagonist IVF protocol. Trial registration number is NCT03240159, retrospectively registered on March 08, 2017. Materials and methods: The efficacy of a single-dose long-acting antagonist, degarelix, was explored initially in healthy donors and subsequently in infertile patients...
2018: Frontiers in Endocrinology
V Vasilca, A Sadeghpour, S Rawson, L E Hawke, S A Baldwin, T Wilkinson, D Bannister, V L G Postis, M Rappolt, S P Muench, L J C Jeuken
Screening assays performed against membrane protein targets (e.g. phage display) are hampered by issues arising from protein expression and purification, protein stability in detergent solutions and epitope concealment by detergent micelles. Here, we have studied a fast and simple method to improve screening against membrane proteins: spherical-supported bilayer lipid membranes ("SSBLM"). SSBLMs can be quickly isolated via low-speed centrifugation and redispersed in liquid solutions while presenting the target protein in a native-like lipid environment...
March 12, 2018: Analytical Biochemistry
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