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https://www.readbyqxmd.com/read/28640691/the-nesprin-cytoskeleton-interface-probed-directly-on-single-nuclei-is-a-mechanically-rich-system
#1
Daniel A Balikov, Sonia K Brady, Ung Hyun Ko, Jennifer H Shin, Jose M de Pereda, Arnoud Sonnenberg, Hak-Joon Sung, Matthew J Lang
The cytoskeleton provides structure and plays an important role in cellular function such as migration, resisting compression forces, and transport. The cytoskeleton also reacts to physical cues such as fluid shear stress or extracellular matrix remodeling by reorganizing filament associations, most commonly focal adhesions and cell-cell cadherin junctions. These mechanical stimuli can result in genome-level changes, and the physical connection of the cytoskeleton to the nucleus provides an optimal conduit for signal transduction by interfacing with nuclear envelope proteins, called nesprins, within the LINC (linker of the nucleus to the cytoskeleton) complex...
June 22, 2017: Nucleus
https://www.readbyqxmd.com/read/28628199/measuring-cancer-drug-sensitivity-and-resistance-in-cultured-cells
#2
Mario Niepel, Marc Hafner, Mirra Chung, Peter K Sorger
Measuring the potencies of small-molecule drugs in cell lines is a critical aspect of preclinical pharmacology. Such experiments are also prototypical of high-throughput experiments in multi-well plates. The procedure is simple in principle, but many unrecognized factors can affect the results, potentially making data unreliable. The procedures for measuring drug response described here were developed by the NIH LINCS program to improve reproducibility. Key features include maximizing uniform cell growth during the assay period, accounting for the effects of cell density on response, and correcting sensitivity measures for differences in proliferation rates...
June 19, 2017: Current Protocols in Chemical Biology
https://www.readbyqxmd.com/read/28625779/multiple-isoforms-of-nesprin1-are-integral-components-of-ciliary-rootlets
#3
Chloe Potter, Wanqiu Zhu, David Razafsky, Philip Ruzycki, Alexander V Kolesnikov, Teresa Doggett, Vladimir J Kefalov, Ewelina Betleja, Moe R Mahjoub, Didier Hodzic
SYNE1 (synaptic nuclear envelope 1) encodes multiple isoforms of Nesprin1 (nuclear envelope spectrin 1) that associate with the nuclear envelope (NE) through a C-terminal KASH (Klarsicht/Anc1/Syne homology) domain (Figure 1A) [1-4]. This domain interacts directly with the SUN (Sad1/Unc84) domain of Sun proteins [5-7], a family of transmembrane proteins of the inner nuclear membrane (INM) [8, 9], to form the so-called LINC complexes (linkers of the nucleoskeleton and cytoskeleton) that span the entire NE and mediate nuclear positioning [10-12]...
June 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28620042/long-noncoding-rnas-lincs-between-human-health-and-disease
#4
REVIEW
Zhi Hao Kwok, Yvonne Tay
Long noncoding RNAs (lncRNAs) represent one of the largest classes of transcripts and are highly diverse in terms of characteristics and functions. Advances in high-throughput sequencing platforms have enabled the rapid discovery and identification of lncRNAs as key regulatory molecules involved in various cellular processes and their dysregulation in various human diseases. Here, we summarize the current knowledge of the functions and underlying mechanisms of lncRNA activity with a particular focus on cancer biology...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28611034/the-missing-linc-for-genetic-cardiovascular-disease
#5
EDITORIAL
Megan J Puckelwartz
No abstract text is available yet for this article.
June 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28586283/mkl1-dependent-gene-activation-is-sufficient-to-induce-actin-cap-assembly
#6
Ketan Thakar, Christopher W Carroll
Actin-dependent forces mechanically control both the position and shape of the nucleus. While the mechanisms that establish nuclear position are well defined, less understood is how actin filaments determine nuclear shape. We recently showed that nuclear envelope-spanning LINC complexes promote stress fiber assembly by activating the small GTPase RhoA and Mkl1-dependent gene activation. We now report that a subset of these stress fibers associate with the apical face of the nuclear envelope through LINC complexes that contain the inner nuclear membrane protein Sun2...
June 6, 2017: Small GTPases
https://www.readbyqxmd.com/read/28580169/endogenous-mirna-sponge-lincrna-ror-promotes-proliferation-invasion-and-stem-cell-like-phenotype-of-pancreatic-cancer-cells
#7
Zhiqiang Fu, Guolin Li, Zhihua Li, Yingxue Wang, Yue Zhao, Shangyou Zheng, Huilin Ye, Yuming Luo, Xiaohui Zhao, Lusheng Wei, Yimin Liu, Qing Lin, Quanbo Zhou, Rufu Chen
The long intergenic non-coding RNA, regulator of reprogramming (linc-ROR) is an oncogene and plays a key role in the embryonic stem cell maintenance and is involved in cancer progression. The objective of this study was to analyze linc-ROR expression in pancreatic ductal adenocarcinoma (PDAC) and determine the regulation effects of linc-ROR on proliferation and invasion of cancer cells, as well as properties of cancer stem-like cells (CSLCs). In this study, we found that linc-ROR was up-regulated in PDAC tissues and related to poor prognosis...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28580009/the-emerging-role-of-the-cytoskeleton-in-chromosome-dynamics
#8
REVIEW
Maya Spichal, Emmanuelle Fabre
Chromosomes underlie a dynamic organization that fulfills functional roles in processes like transcription, DNA repair, nuclear envelope stability, and cell division. Chromosome dynamics depend on chromosome structure and cannot freely diffuse. Furthermore, chromosomes interact closely with their surrounding nuclear environment, which further constrains chromosome dynamics. Recently, several studies enlighten that cytoskeletal proteins regulate dynamic chromosome organization. Cytoskeletal polymers that include actin filaments, microtubules and intermediate filaments can connect to the nuclear envelope via Linker of the Nucleoskeleton and Cytoskeleton (LINC) complexes and transfer forces onto chromosomes inside the nucleus...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28576601/linc-ing-the-noncoding-genome-to-heart-function-beating-hypertrophy
#9
Shambhabi Chatterjee, Christian Bär, Thomas Thum
The principal event of aberrant gene expression occurs in numerous disorders and syndromes, including heart failure. LncRNAs may constitute powerful treatment targets because they intensively interact with their genetic environment, as they are important regulators of genetic networks. Recent advances on the functional roles of lncRNAs in cardiac hypertrophy are expected to usher improved therapeutic strategies.
May 30, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28533284/nesprin-1%C3%AE-2-is-essential-for-mouse-postnatal-viability-and-nuclear-positioning-in-skeletal-muscle
#10
Matthew J Stroud, Wei Feng, Jianlin Zhang, Jennifer Veevers, Xi Fang, Larry Gerace, Ju Chen
The position of the nucleus in a cell is controlled by interactions between the linker of nucleoskeleton and cytoskeleton (LINC) complex and the cytoskeleton. Defects in nuclear positioning and abnormal aggregation of nuclei occur in many muscle diseases and correlate with muscle dysfunction. Nesprin 1, which includes multiple isoforms, is an integral component of the LINC complex, critical for nuclear positioning and anchorage in skeletal muscle, and is thought to provide an essential link between nuclei and actin...
May 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28493118/position-matters-multiple-functions-of-linc-dependent-chromosome-positioning-during-meiosis
#11
Kazuhiro Katsumata, Eriko Nishi, Sadia Afrin, Kaoru Narusawa, Ayumu Yamamoto
Chromosome positioning is crucial for multiple chromosomal events, including DNA replication, repair, and recombination. The linker of nucleoskeleton and cytoskeleton (LINC) complexes, which consist of conserved nuclear membrane proteins, were shown to control chromosome positioning and facilitate various biological processes by interacting with the cytoskeleton. However, the precise functions and regulation of LINC-dependent chromosome positioning are not fully understood. During meiosis, the LINC complexes induce clustering of telomeres, forming the bouquet chromosome arrangement, which promotes homologous chromosome pairing...
May 10, 2017: Current Genetics
https://www.readbyqxmd.com/read/28492570/-the-use-of-mechanical-chest-compression-devices-for-both-out-of-hospital-and-in-hospital-refractory-cardiac-arrest
#12
Alessandra Russo, Nicola Gasparetto, Luca Favero, Salvatore Ivan Caico, Silvia Orazio, Guido Garzena, Paolo Rosi, Zoran Olivari
The purpose of cardiopulmonary resuscitation after sudden cardiac arrest is to restore minimal blood flow to provide oxygen to the brain and other vital organs. Chest compressions and external defibrillation are the first line for circulatory support. Although early defibrillation is the main factor influencing survival, cardiopulmonary resuscitation must be characterized by high-quality external chest compressions. Unfortunately, the performance of manual chest compressions decreases during time and in hostile conditions...
April 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28473307/the-rsvp-project-factors-related-to-disengagement-from-human-immunodeficiency-virus-care-among-persons-in-san-francisco
#13
Susan Scheer, Miao-Jung Chen, Maree Kay Parisi, Maya Yoshida-Cervantes, Erin Antunez, Viva Delgado, Nicholas J Moss, Kate Buchacz
BACKGROUND: In the United States, an estimated two-thirds of persons with human immunodeficiency virus (HIV) infection do not achieve viral suppression, including those who have never engaged in HIV care and others who do not stay engaged in care. Persons with an unsuppressed HIV viral load might experience poor clinical outcomes and transmit HIV. OBJECTIVE: The goal of the Re-engaging Surveillance-identified Viremic Persons (RSVP) project in San Francisco, CA, was to use routine HIV surveillance databases to identify, contact, interview, and reengage in HIV care persons who appeared to be out of care because their last HIV viral load was unsuppressed...
May 4, 2017: JMIR Public Health and Surveillance
https://www.readbyqxmd.com/read/28472897/the-anticancer-effect-of-mebendazole-may-be-due-to-m1-monocyte-macrophage-activation-via-erk1-2-and-tlr8-dependent-inflammasome-activation
#14
Kristin Blom, Wojciech Senkowski, Malin Jarvius, Malin Berglund, Jenny Rubin, Lena Lenhammar, Vendela Parrow, Claes Andersson, Angelica Loskog, Mårten Fryknäs, Peter Nygren, Rolf Larsson
Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation...
May 4, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28463330/improving-the-performance-of-interferometric-imaging-through-the-use-of-disturbance-feedforward
#15
Michael Böhm, Martin Glück, Alexander Keck, Jörg-Uwe Pott, Oliver Sawodny
In this paper, we present a disturbance compensation technique to improve the performance of interferometric imaging for extremely large ground-based telescopes, e.g., the Large Binocular Telescope (LBT), which serves as the application example in this contribution. The most significant disturbance sources at ground-based telescopes are wind-induced mechanical vibrations in the range of 8-60 Hz. Traditionally, their optical effect is eliminated by feedback systems, such as the adaptive optics control loop combined with a fringe tracking system within the interferometric instrument...
May 1, 2017: Journal of the Optical Society of America. A, Optics, Image Science, and Vision
https://www.readbyqxmd.com/read/28455503/lamins-and-nesprin-1-mediate-inside-out-mechanical-coupling-in-muscle-cell-precursors-through-fhod1
#16
Christine Schwartz, Martina Fischer, Kamel Mamchaoui, Anne Bigot, Thevy Lok, Claude Verdier, Alain Duperray, Richard Michel, Ian Holt, Thomas Voit, Suzanna Quijano-Roy, Gisèle Bonne, Catherine Coirault
LINC complexes are crucial for the response of muscle cell precursors to the rigidity of their environment, but the mechanisms explaining this behaviour are not known. Here we show that pathogenic mutations in LMNA or SYNE-1 responsible for severe muscle dystrophies reduced the ability of human muscle cell precursors to adapt to substrates of different stiffness. Plated on muscle-like stiffness matrix, mutant cells exhibited contractile stress fibre accumulation, increased focal adhesions, and higher traction force than controls...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28448008/a-protocol-for-using-f%C3%A3-rster-resonance-energy-transfer-fret-force-biosensors-to-measure-mechanical-forces-across-the-nuclear-linc-complex
#17
Paul T Arsenovic, Kranthidhar Bathula, Daniel E Conway
The LINC complex has been hypothesized to be the critical structure that mediates the transfer of mechanical forces from the cytoskeleton to the nucleus. Nesprin-2G is a key component of the LINC complex that connects the actin cytoskeleton to membrane proteins (SUN domain proteins) in the perinuclear space. These membrane proteins connect to lamins inside the nucleus. Recently, a Förster Resonance Energy Transfer (FRET)-force probe was cloned into mini-Nesprin-2G (Nesprin-TS (tension sensor)) and used to measure tension across Nesprin-2G in live NIH3T3 fibroblasts...
April 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28443494/expression-profiling-of-long-non-coding-rna-identifies-linc-ror-as-a-prognostic-biomarker-in-oral-cancer
#18
Ganesan Arunkumar, Arunagiri Kuha Deva Magendhra Rao, Mayakannan Manikandan, Kanagaraj Arun, Vilvanathan Vinothkumar, Sundaramoorthy Revathidevi, Kottayasamy Seenivasagam Rajkumar, Ramamurthy Rajaraman, Arasambattu Kannan Munirajan
Oral squamous cell carcinoma is the most aggressive cancer that is associated with high recurrence, metastasis, and poor treatment outcome. Dysregulation of long non-coding RNAs has been shown to promote tumor growth and metastasis in several cancers. In this study, we investigated the expression of 11 selected long non-coding RNAs that are associated with cell proliferation, metastasis, and tumor suppression in oral squamous cell carcinomas and normal tissues by quantitative real-time polymerase chain reaction...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28430799/diagnostic-and-prognostic-value-of-long-noncoding-rnas-as-biomarkers-in-urothelial-carcinoma
#19
Johanna Droop, Tibor Szarvas, Wolfgang A Schulz, Christian Niedworok, Günter Niegisch, Kathrin Scheckenbach, Michèle J Hoffmann
Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106)...
2017: PloS One
https://www.readbyqxmd.com/read/28415684/the-long-noncoding-rna-linc-ned125-controls-the-expression-of-medulloblastoma-driver-genes-by-microrna-sponge-activity
#20
Pietro Laneve, Agnese Po, Annarita Favia, Ivano Legnini, Vincenzo Alfano, Jessica Rea, Valerio Di Carlo, Valeria Bevilacqua, Evelina Miele, Angela Mastronuzzi, Andrea Carai, Franco Locatelli, Irene Bozzoni, Elisabetta Ferretti, Elisa Caffarelli
Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease-related gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissue-specificity makes them attractive candidates as diagnostic/prognostic biomarkers and/or therapeutic agents. Here we show that linc-NeD125, which we previously characterized as a neuronal-induced lncRNA, is significantly overexpressed in Group 4 medulloblastomas (G4 MBs), the largest and least well characterized molecular MB subgroup...
May 9, 2017: Oncotarget
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