8 research outputs found

    Active restructuring of cytoskeleton composites leads to increased mechanical stiffness, memory, and heterogeneity

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    The composite cytoskeleton, comprising interacting networks of semiflexible actin and rigid microtubules, actively generates forces and restructures using motor proteins such as myosins to enable key mechanical processes including cell motility and mitosis. Yet, how motor-driven activity alters the mechanics of cytoskeleton composites remains an open challenge. Here, we perform optical tweezers microrheology on actin-microtubule composites driven by myosin II motors to show that motor activity increases the linear viscoelasticity and elastic storage of the composite by active restructuring to a network of tightly-packed filament clusters and bundles. Our nonlinear microrheology measurements performed hours after cessation of activity show that the motor-contracted structure is stable and robust to nonlinear forcing. Unique features of the nonlinear response include increased mechanical stiffness, memory and heterogeneity, coupled with suppressed filament bending following motor-driven restructuring. Our results shed important new light onto the interplay between viscoelasticity and non-equilibrium dynamics in active polymer composites such as the cytoskeleton

    Reorganization of complex ciliary flows around regenerating Stentor coeruleus

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    © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Wan, K. Y., Hurlimann, S. K., Fenix, A. M., McGillivary, R. M., Makushok, T., Burns, E., Sheung, J. Y., & Marshall, W. F. Reorganization of complex ciliary flows around regenerating Stentor coeruleus. Philosophical Transactions of the Royal Society of London.Series B, Biological Sciences, 375(1792), (2020): 20190167, doi: 10.1098/rstb.2019.0167.The phenomenon of ciliary coordination has garnered increasing attention in recent decades and multiple theories have been proposed to explain its occurrence in different biological systems. While hydrodynamic interactions are thought to dictate the large-scale coordinated activity of epithelial cilia for fluid transport, it is rather basal coupling that accounts for synchronous swimming gaits in model microeukaryotes such as Chlamydomonas. Unicellular ciliates present a fascinating yet understudied context in which coordination is found to persist in ciliary arrays positioned across millimetre scales on the same cell. Here, we focus on the ciliate Stentor coeruleus, chosen for its large size, complex ciliary organization, and capacity for cellular regeneration. These large protists exhibit ciliary differentiation between cortical rows of short body cilia used for swimming, and an anterior ring of longer, fused cilia called the membranellar band (MB). The oral cilia in the MB beat metachronously to produce strong feeding currents. Remarkably, upon injury, the MB can be shed and regenerated de novo. Here, we follow and track this developmental sequence in its entirety to elucidate the emergence of coordinated ciliary beating: from band formation, elongation, curling and final migration towards the cell anterior. We reveal a complex interplay between hydrodynamics and ciliary restructuring in Stentor, and highlight for the first time the importance of a ring-like topology for achieving long-range metachronism in ciliated structures.We gratefully acknowledge financial support from the Marine Biology Laboratory at Woods Hole, MA, NIH grant no. R35 GM097017 (W.F.M.) and the University of Exeter, UK (K.Y.W.)

    Structural Contributions to Hydrodynamic Diameter for Quantum Dots Optimized for Live-Cell Single-Molecule Tracking

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    Quantum dots are fluorescent nanoparticles with narrow-band, size-tunable, and long-lasting emission. Typical formulations used for imaging proteins in cells are hydrodynamically much larger than the protein targets, so it is critical to assess the impact of steric effects deriving from hydrodynamic size. This report analyzes a new class of quantum dots that have been engineered for minimized size specifically for imaging receptors in narrow synaptic junctions between neurons. We use fluorescence correlation spectroscopy and transmission electron microscopy to calculate the contributions of the crystalline core, organic coating, and targeting proteins (streptavidin) to the total hydrodynamic diameter of the probe, using a wide range of core materials with emission spanning 545–705 nm. We find the contributing thickness of standard commercial amphiphilic polymers to be ∼8 to ∼14 nm, whereas coatings based on the compact ligand HS-(CH<sub>2</sub>)<sub>11</sub>-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>4</sub>-OH contribute ∼6 to ∼9 nm, reducing the diameter by ∼2 to ∼5 nm, depending on core size. When the number of streptavidins for protein targeting is minimized, the total diameter can be further reduced by ∼5 to ∼11 nm, yielding a diameter of 13.8–18.4 nm. These findings explain why access to the narrow synapse derive primarily from the protein functionalization of commercial variants, rather than the organic coating layers. They also explain why those quantum dots with size around 14 nm with only a few streptavidins can access narrow cellular structures for neuronal labeling, whereas those >27 nm and a large number of streptavidins, cannot

    Kinesin and Myosin Motors Compete to Drive Rich Multi-Phase Dynamics in Programmable Cytoskeletal Composites

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    The cytoskeleton of biological cells relies on a diverse population of motors, filaments, and binding proteins acting in concert to enable non-equilibrium processes ranging from mitosis to chemotaxis. The cytoskeleton's versatile reconfigurability, programmed by interactions between its constituents, make it a foundational active matter platform. However, current active matter endeavors are limited largely to single force-generating components acting on a single substrate - far from the composite cytoskeleton in live cells. Here, we engineer actin-microtubule composites, driven by kinesin and myosin motors and tuned by crosslinkers, that restructure into diverse morphologies from interpenetrating filamentous networks to de-mixed amorphous clusters. Our Fourier analyses reveal that kinesin and myosin compete to delay kinesin-driven restructuring and suppress de-mixing and flow, while crosslinking accelerates reorganization and promotes actin-microtubule correlations. The phase space of non-equilibrium dynamics falls into three broad classes - slow reconfiguration, fast advective flow, and multi-mode ballistic dynamics - with structure-dynamics relations described by the relative contributions of elastic and dissipative responses to motor-generated strain

    Proceedings Of The 7Th Biannual International Symposium On Nasopharyngeal Carcinoma 2015

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    A1 Hope and despair in the current treatment of nasopharyngeal cancer, IB Tan, I1 NPC international incidence and risk factors, Ellen T Chang, I2 Familial nasopharyngeal carcinoma and the use of biomarkers, Chien-Jen Chen, Wan-Lun Hsu, Yin-Chu Chien, I3 Genetic susceptibility risk factors for sporadic and familial NPC: recent findings, Allan Hildesheim, I5 Genetic and environmental risk factors for nasopharyngeal cancer in Southeast Asia, James D McKay, Valerie Gaborieau, Mohamed Arifin Bin Kaderi, Dewajani Purnomosari, Catherine Voegele, Florence LeCalvez-Kelm, Graham Byrnes, Paul Brennan, Beena Devi, I6 Characterization of the NPC methylome identifies aberrant epigenetic disruption of key signaling pathways and EBV-induced gene methylation, Li L, Zhang Y, Fan Y, Sun K, Du Z, Sun H, Chan AT, Tsao SW, Zeng YX, Tao Q, I7 Tumor exosomes and translational research in NPC, Pierre Busson, Claire Lhuillier, Olivier Morales, Dhafer Mrizak, Aurore Gelin, Nikiforos Kapetanakis, Nadira Delhem, I8 Host manipulations of the Epstein-Barr virus EBNA1 protein, Sheila Mansouri, Jennifer Cao, Anup Vaidya, and Lori Frappier, I9 Somatic genetic changes in EBV-associated nasopharyngeal carcinoma, Lo Kwok Wai, I10 Preliminary screening results for nasopharyngeal carcinoma with ELISA-based EBV antibodies in Southern China, Sui-Hong Chen, Jin-lin Du, Ming-Fang Ji, Qi-Hong Huang, Qing Liu, Su-Mei Cao, I11 EBV array platform to screen for EBV antibodies associated with NPC and other EBV-associated disorders, Denise L. Doolan, Anna Coghill, Jason Mulvenna, Carla Proietti, Lea Lekieffre, Jeffrey Bethony, and Allan Hildesheim, I12 The nasopharyngeal carcinoma awareness program in Indonesia, Renske Fles, Sagung Rai Indrasari, Camelia Herdini, Santi Martini, Atoillah Isfandiari, Achmad Rhomdoni, Marlinda Adham, Ika Mayangsari, Erik van Werkhoven, Maarten Wildeman, Bambang Hariwiyanto, Bambang Hermani, Widodo Ario Kentjono, Sofia Mubarika Haryana, Marjanka Schmidt, IB Tan, I13 Current advances and future direction in nasopharyngeal cancer management, Brian O’Sullivan, I14 Management of juvenile nasopharyngeal cancer, Enis Ozyar, I15 Global pattern of nasopharyngeal cancer: correlation of outcome with access to radiotherapy, Anne WM Lee, I16 The predictive/prognostic biomarker for nasopharyngeal carcinoma, Mu-Sheng Zeng, I17 Effect of HLA and KIR polymorphism on NPC risk, Xiaojiang Gao, Minzhong Tang, Pat Martin, Yi Zeng, Mary Carrington, I18 Exploring the Association between Potentially Neutralizing Antibodies against EBV Infection and Nasopharyngeal Carcinoma, Anna E Coghill, Wei Bu, Hanh Nguyen, Wan-Lun Hsu, Kelly J Yu, Pei-Jen Lou, Cheng-Ping Wang, Chien-Jen Chen, Allan Hildesheim, Jeffrey I Cohen, I19 Advances in MR imaging in NPC, Ann D King, O1 Epstein-Barr virus seromarkers and risk of nasopharyngeal carcinoma: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan, Yin-Chu Chien, Wan-Lun Hsu, Kelly J Yu, Tseng-Cheng Chen, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Laio, Yen-Liang Chang, Cheng-Ping Wang, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan Lee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Pei-Jen Lou, Allan Hildesheim, Chien-Jen Chen, O2 Familial tendency and environmental co-factors of nasopharyngeal carcinoma: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan, Wan-Lun Hsu, Kelly J Yu, Yin-Chu Chien, Tseng-Cheng Chen, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Liao, Yen-Liang Chang, Tsung-Lin Yang, Chun-Hun Hua, Ming-ShiangWu, Chu-Hsing Kate Hsiao, Jehn-ChuanLee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Jenq-Yuh Ko, Allan Hildesheim, Chien-Jen Chen, O3 The genetic susceptibility and prognostic role of TERT-CLPTM1L and genes in DNA damage pathways in NPC, Josephine Mun Yee Ko, Wei Dai, Dora Kwong, Wai Tong Ng, Anne Lee, Roger Kai Cheong Ngan, Chun Chung Yau, Stewart Tung, Maria Li Lung, O4 Long term effects of NPC screening, Mingfang Ji, Wei Sheng, Mun Hon Ng, Weimin Cheng, Xia Yu, Biaohua Wu, Kuangrong Wei, Jun Zhan, Yi Xin Zeng, Su Mei Cao, Ningshao Xia, Yong Yuan, O5 Risk prediction of nasopharyngeal carcinoma by detecting host genetic and Epstein-Barr virus variation in saliva, Qian Cui, Miao Xu, Jin-Xin Bei, Yi-Xin Zeng, O6 Patterns of care study in Turkish nasopharyngeal cancer patients (NAZOTURK): A Turkish Radiation Oncology Association Head and Neck Cancer Working Group Study, B Şahin, A Dizman, M Esassolak, A Saran İkizler, HC Yıldırım, M Çaloğlu, B Atalar, F Akman, C Demiroz, BM Atasoy, E Canyilmaz, S Igdem, G Ugurluer, T Kütük, M Akmansoy, E Ozyar, O7 Long term outcome of intensity modulated radiotherapy in nasopharyngeal carcinoma in National Cancer Centre Singapore, Kiattisa Sommat, Fu Qiang Wang, Li-Lian Kwok, Terence Tan, Kam Weng Fong, Yoke Lim Soong, Shie Lee Cheah, Joseph Wee, O8 International phase II randomized study on the addition of docetaxel to the combination of cisplatin and 5-fluorouracil in the induction treatment for nasopharyngeal carcinoma in children and adolescents, M Casanova, E Özyar, C Patte, D Orbach, A Ferrari, VF Cristine, H Errihani, J Pan, L Zhang, S Liji, K Grzegorzewski, L Gore, A Varan, O9 Prognostic impact of metastatic status in patients with nasopharyngeal carcinoma, Susanna Hilda Hutajulu, Guntara Khuzairi, Camelia Herdini, Henry Kusumo, Mardiah Suci Hardianti, Kartika Widayati Taroeno-Hariadi, Ibnu Purwanto, Johan Kurnianda, O10 Development of small molecule inhibitors of latent Epstein-Barr virus infection for the treatment of nasopharyngeal carcinoma, Troy E. Messick, Kimberly Malecka, Lois Tolvinski, Samantha Soldan, Julianna Deakyne, Hui Song, Antonio van den Heuvel, Baiwei Gu, Joel Cassel, Mark McDonnell, Garry R Smith, Venkata Velvadapu, Haiyan Bian, Yan Zhang, Marianne Carlsen, Shuai Chen, Alastair Donald, Christian Lemmen, Allen B Reitz, Paul M Lieberman, O11 Therapeutic targeting of cancer stem-like cells using a Wnt modulator, ICG-001, enhances the treatment outcome of EBV-positive nasopharyngeal carcinoma, King Chi Chan, Lai Sheung Chan, Kwok Wai Lo, Timothy Tak Chun Yip, Roger Kai Cheong Ngan, Michael Kahn, Maria Li Lung, Nai Ki Mak, O12 Role of micro-RNA in NPC biology, Fei-Fei Liu, O13 Expansion of EBNA1- and LMP2-specific effector T lymphocytes from patients with nasopharyngeal carcinoma without enhancement of regulatory T cells, Wafa Khaali; Juliette Thariat; Laurence Fantin; Flavia Spirito; Meriem Khyatti; El Khalil Ben Driss; Sylvain Olivero; Janet Maryanski; Alain Doglio, O14 The experience of patients’ life after amifostine radiotherapy treatment (ART) for nasopharyngeal carcinoma (NPC), Mengxue Xia, Yunfei Xia, Hui Chang, Rachel Shaw, O15 Analysis of mitochondrial DNA mutation in latent membrane protein-1 positive nasopharyngeal carcinoma, Pudji Rahaju, O16 Factors influencing treatment adherence of nasopharyngeal cancer and the clinical outcomes: a hospital-based study, Mardiah Suci Hardianti, Sindhu Wisesa, Kartika Widayati Taroeno-Harijadi, Ibnu Purwanto, Bambang Hariwiyanto, Wigati Dhamiyati, Johan Kurnianda, O17 Chromosomal breaks mediated by bile acid-induced apoptosis in nasopharyngeal epithelial cells: in relation to matrix association region/scaffold attachment region, Sang-Nee Tan, Sai-Peng Sim, O18 Expression of p53 (wild type) on nasopharyngeal carcinoma stem cell that resistant to radiotherapy, Muhtarum Yusuf, Ahmad C Romdhoni, Widodo Ario K, Fedik Abdul Rantam, O19 Mathematical model of nasopharyngeal carcinoma in cellular level, Sugiyanto, Lina Aryati, Fajar Adi-Kusumo, Mardiah Suci Hardianti, O20 Differential expression of microRNA-21 on nasopharyngeal carcinoma plasma patient, SY Bintoro, R Oktriani, C. Herawati, A Surono, Sofia M. Haryana, O21 Therapeutic targeting of an oncogenic fibroblast growth factor-FGF19, which promotes proliferation and induces EMT of carcinoma cells through activating ERK and AKT signaling, L. Zhong, L. Li, B. B. Ma, A. T. Chan, Q. Tao, O22 Resist nasopharyngeal carcinoma (NPC): next generation T cells for the adoptive immunotherapy of NPC, M. Kalra, M. Ngo, S. Perna, A. Leen, N. Lapteva, C. M. Rooney, S. Gottschalk, O23 The correlation of heat shock protein 70 expressions and staging of nasopharyngeal carcinoma, Elida Mustikaningtyas, Sri Herawati, Achmad C Romdhoni, O24 Epstein-Barr virus serological profiles of nasopharyngeal carcinoma - A tribute to Werner Henle, Mingfang Ji, YaruiXu, Weimin Cheng, ShengxiangGe, Fugui Li, M. H. Ng, O25 Targeting the apoptosis pathway using combination TLR3 agonist with anti-survivin molecule (YM-155) in nasopharyngeal carcinoma, Louise SY Tan, Benjamin Wong, CM Lim, O26 The resistance mechanism of nasopharyngeal cancer stem cells to cisplatin through expression of CD44, Hsp70, p53 (wild type), Oct-4, and ß-catenin encoded-genes, Achmad C Romdhoni, Fedik A. Rantam, Widodo Ario Kentjono, P1 Prevalence of nasopharyngeal carcinoma patients at Departement of Otorhinolaringology-Head and Neck Surgery, Dr. Hasan Sadikin general hospital, Bandung, Indonesia in 2010-2014, Deasy Z Madani, Nur Akbar, Agung Dinasti Permana, P2 Case report on pediatric nasopharyngeal carcinoma at Dr. Sardjito Hospital, Yogyakarta, Camelia Herdini, Sagung Rai Indrasari, Jajah Fachiroh, Dwi Hartati, T. Baning Rahayudjati, P3 Report on loco regionally advanced nasopharyngeal cancer patients treated with induction chemotherapy followed by concurrent chemo-radiation therapy, Iswandi Darwis, Susanna Hilda Hutajulu, Bambang Hariwiyanto, Wigati Dhamiyati, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P4 Sex and age differences in the survival of patients with nasopharyngeal carcinoma, Sindhu Wisesa, Mardiah Suci Hardianti, Susanna Hilda Hutajulu, Kartika Widayati Taroeno-Harijadi, Ibnu Purwanto, Camelia Herdini, Wigati Dhamiyati, Johan Kurnianda, P5 Impact of delayed diagnosis and delayed therapy in the treatment outcome of patients with nasopharyngeal carcinoma, Khoirul Anwar, Susanna Hilda Hutajulu, Sagung Rai Indrasari, Sri Retna Dwidanarti, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P6 Anaysis of pretreatment anemia in nasopharyngeal cancer patients undergoing neoadjuvant therapy, Dominicus Wendhy Pramana, Susanna Hilda Hutajulu, Bambang Hariwiyanto, Wigati Dhamiyati, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P7 Results of treatment with neoadjuvant cisplatin-5FU in locally advanced nasopharyngeal carcinoma: a local experience, Diah Ari Safitri, Susanna Hilda Hutajulu, Camelia Herdini, Sri Retna Dwi Danarti, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P8 Geriatrics with nasopharyngeal cancer, Suryo A Taroeno, Sindhu Wisesa, Kartika Widayati Taroeno-Hariadi, Ibnu Purwanto, Bambang Hariwiyanto, Wigati Dhamiyati, Johan Kurnianda, P9 Correlation of lymphocyte to monocyte and neutrophil to lymphocyte ratio to the response of cisplatin chemoradiotheraphy in locally advance nasopharyngeal carcinoma, I. Wijaya, A. Oehadian, D. Prasetya, P10 Prediction of nasopharyngeal carcinoma risk by Epstein-Barr virus seromarkers and environmental co-factors: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan, Wan-Lun Hsu, Yin-Chu Chien, Kelly J Yu, Cheng-Ping Wang, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Liao, Yen-Liang Chang191,192, Jenq-Yuh Ko, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan Lee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Pei-Jen Lou, Allan Hildesheim, Chien-Jen Chen, P11 Non-viral risk factors for nasopharyngeal carcinoma in West Sumatra, Indonesia, Sukri Rahman, Bestari J. Budiman, Novialdi, Rahmadona, Dewi Yuri Lestari, P12 New prototype Vidas EBV IgA quick: performance on Chinese and Moroccan populations, C. Yin, A. Foussadier, E. Blein, C. Chen, N. Bournet Ammour, M. Khiatti, S. Cao, P13 The expression of EBV-LMP1 and VEGF as predictors and plasma EBV-DNA levels as early marker of distant metastasis after therapy in nasopharyngeal cancer, Dewi Syafriyetti Soeis Marzaini, P14 Characteristics and factors influencing subjects refusal for blood samples retrieval: lesson from NPC case control study in Yogyakarta – Indonesia, Dwi Hartati, Baning Rahayujati, Camelia Herdini, Jajah Fachiroh, P15 Expression of microRNA BART-7-3p and mRNA PTEN on blood plasma of patients with nasopharyngeal carcinoma, L. Gunawan, S. Mubarika Haryana, A. Surono, C. Herawati, P16 IgA response to native early antigen (IgA-EAext) of Epstein-Barr virus (EBV) in healthy population and nasopharyngeal carcinoma (NPC) patients: the potential for diagnosis and screening tools, Michael Hartono, Jajah Fachiroh, Umi Intansari, Dewi Kartikawati Paramita, P17 IgA responses against Epstein-Barr Virus Early Antigen (EBV-EA) peptides as potential candidates of nasopharyngeal carcinoma detection marker, Akmal Akbar, Jajah Fachiroh, Dewi Kartikawati Paramita, P18 Association between smoking habit and IgA-EBV titer among healthy individuals in Yogyakarta, Indonesia, Benny Hermawan, T Baning Rahayudjati, Dewi K Paramita, Jajah Fachiroh, P19 Epstein-Barr virus IgA titer comparison of healthy non-family individuals and healthy first degree family of NPV patients, Gabriella Argy, Jajah Fachiroh, Dewi Kartikawati Paramita, Susanna Hilda Hutajulu, P20 Identification of EBV Early Antigen (EA) derived peptides for NPC diagnosis, Theodora Caroline Sihotang, Jajah Fachiroh, Umi Intansari, Dewi Kartikawati Paramita, P21 Host-pathogen study: relative expression of mRNA BRLF1 Epstein-Barr virus as a potential biomarker for tumor progressivity and polymorphisms of TCRBC and TCRGC2 host genes related to genetic susceptibility on nasopharyngeal carcinoma, Daniel Joko Wahyono, Purnomo Soeharso, Dwi Anita Suryandari, Lisnawati, Zanil Musa, Bambang Hermani, P22 In vitro efficacy of silvestrol and episilvestrol, isolated from Borneo, on nasopharyngeal carcinoma, a major cancer in Borneo, Maelinda Daker, Yeo Jiun Tzen, Norhasimah Bakar, Asma’ Saiyidatina Aishah Abdul Rahman, Munirah Ahmad, Yeo Tiong Chia, Alan Khoo Soo Beng, P23 The expression of mir-141 in patients with nasopharyngeal cancer, Widyandani Sasikirana, Tirta Wardana, Muhammad Radifar, Cita Herawati, Agus Surono, Sofia Mubarika HaryanaPubMe
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