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Zeinab Jahed, Darya Fadavi, Uyen T Vu, Ehsaneddin Asgari, G W Gant Luxton, Mohammad R K Mofrad
The LINC complex is found in a wide variety of organisms and is formed by the transluminal interaction between outer- and inner-nuclear-membrane KASH and SUN proteins, respectively. Most extensively studied are SUN1 and SUN2 proteins, which are widely expressed in mammals. Although SUN1 and SUN2 play functionally redundant roles in several cellular processes, more recent studies have revealed diverse and distinct functions for SUN1. While several recent in vitro structural studies have revealed the molecular details of various fragments of SUN2, no such structural information is available for SUN1...
March 13, 2018: Biophysical Journal
You Kure Wu, Hiroki Umeshima, Junko Kurisu, Mineko Kengaku
Nuclear migration of newly born neurons is essential for cortex formation in the brain. The nucleus is translocated by actin and microtubules, yet the actual force generated by the interplay of these cytoskeletons remains elusive. High-resolution time-lapse observation of migrating murine cerebellar granule cells revealed that the nucleus actively rotates along the direction of its translocation, independently of centrosome motion. Pharmacological and molecular perturbation indicated that spin torque is primarily generated by microtubule motors through the LINC complex in the absence of actomyosin contractility...
March 8, 2018: Development
Jared Hennen, Cosmo A Saunders, Joachim D Mueller, G W Gant Luxton
Linker of nucleoskeleton and cytoskeleton (LINC) complexes are conserved molecular bridges within the nuclear envelope that mediate mechanical force transmission into the nucleoplasm. The core of the LINC complex is formed by a transluminal interaction between the outer and inner nuclear membrane KASH and SUN proteins, respectively. Mammals encode six KASH proteins and five SUN proteins. Recently, KASH proteins were shown to bind to the domain interfaces of trimeric SUN2 proteins in vitro However neither the existence of SUN2 trimers in living cells nor the extent to which other SUN proteins conform to this assembly state have been tested experimentally...
March 7, 2018: Molecular Biology of the Cell
R Todd Watkins, Linc J Conn, Robert G Gellin, Theresa S Gonzales, Lindsey M Hamil, Monica J Cayouette, Michael G Schmidt
The analysis of dental students' clinical production/participation has been used to assess whether a prospective graduate is capable of unsupervised and independent practice (that is, competent to perform that practice). This method and others have inherent biases that may not accurately reflect whether the student has mastered the associated concepts and techniques required for dentistry. The aim of this study was to assess an informatics system that assigned curriculum meta-tags with time-based relative educational value units (ReVUs) to each clinical procedure performed by Medical University of South Carolina (MUSC) students...
March 2018: Journal of Dental Education
Can Zhou, Li Rao, Catherine M Shanahan, Qiuping Zhang
Nesprins (nuclear envelope spectrin repeat proteins) are multi-isomeric scaffolding proteins. Nesprin-1 and -2 are highly expressed in skeletal and cardiac muscles and together with SUN (Sad1p/UNC84) domain-containing proteins form the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex at the nuclear envelope in association with lamin A/C and emerin. Mutations in nesprin-1/2 have been found in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD) as well as dilated cardiomyopathy (DCM)...
February 27, 2018: Biochemical Society Transactions
Anssi Lipponen, Assam El-Osta, Antony Kaspi, Mark Ziemann, Ishant Khurana, Harikrishnan Kn, Vicente Navarro-Ferrandis, Noora Puhakka, Jussi Paananen, Asla Pitkänen
Traumatic brain injury (TBI) induces a wide variety of cellular and molecular changes that can continue for days to weeks to months, leading to functional impairments. Currently, there are no pharmacotherapies in clinical use that favorably modify the post-TBI outcome, due in part to limited understanding of the mechanisms of TBI-induced pathologies. Our system biology analysis tested the hypothesis that chronic transcriptomics changes induced by TBI are controlled by altered DNA-methylation in gene promoter areas or by transcription factors...
February 27, 2018: Acta Neuropathologica Communications
Hiromasa Imaizumi, Katsutoshi Sato, Asuka Nishihara, Kazumasa Minami, Masahiko Koizumi, Nariaki Matsuura, Miki Hieda
The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various process at the nuclear envelope including nuclear migration, mechanotransduction, chromatin tethering, and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1); a component of the LINC complex functions in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown...
February 21, 2018: Cancer Science
Zichen Wang, Alexander Lachmann, Alexandra B Keenan, Avi Ma'ayan, Oliver Stegle
Motivation: As part of the NIH Library of Integrated Network-based Cellular Signatures (LINCS) program, hundreds of thousands of transcriptomic signatures were generated with the L1000 technology, profiling the response of human cell lines to over 20,000 small molecule compounds. This effort is a promising approach toward revealing the mechanisms-of-action (MOA) for marketed drugs and other less studied potential therapeutic compounds. Results: L1000 fireworks display (L1000FWD) is a web application that provides interactive visualization of over 16,000 drug and small-molecule induced gene expression signatures...
February 6, 2018: Bioinformatics
Brian Burke
Meiosis is a key processes of sexual reproduction in eukaryotes. By combining two cell division cycles with a single round of DNA replication meiosis provides a mechanism to generate haploid gametes. Coincidentally, processes involved in ensuring appropriate segregation of homologous chromosomes also result in genetic recombination and shuffling of genes between each generation. During the first meiotic prophase, rapid telomere-led chromosome movements facilitate alignment and pairing of homologous chromosomes...
January 29, 2018: Current Opinion in Cell Biology
Yang Xu, Wei Li, Huimin Ke, Wei Feng
LINC complexes span across the nuclear envelope and are assembled by SUN and KASH proteins. SUN1 and SUN2 are the two most abundant SUN proteins in mammals. In SUN2, the predicted coiled-coil domain preceding the SUN domain forms a three-helix bundle that constitutes an autoinhibitory domain (AID) to lock down the SUN domain. Here, we found that SUN1 also contains an AID preceding the SUN domain and solved the structure of the AID-SUN tandem of SUN1. SUN1 AID also adopts a three-helix bundle conformation that interacts with the SUN domain and keeps it in an autoinhibited state...
February 3, 2018: Biochemical and Biophysical Research Communications
M Pleaner, C Morroni, J Smit, N Lince-Deroche, M Chersich, S Mullick, D Pillay, M Makua, H Rees
In 2014, South Africa (SA) introduced the subdermal contraceptive implant with the aim of expanding the contraceptive method mix and availability of long-acting reversible methods in the public sector. Three years on, concerns have been raised about the decline in uptake, early implant removals and challenges in service delivery. This article explores the lessons learnt from the introduction of contraceptive technologies elsewhere and applies these to the SA context. Drawing on the World Health Organization’s conceptual framework for the introduction of new contraceptive methods, and subsequent literature on the topic, lessons are classified into six cross-cutting themes...
October 1, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
Daria I Chernego, Robert B McCall, Shannon B Wanless, Christina J Groark, Marina J Vasilyeva, Oleg I Palmov, Natalia V Nikiforova, Rifkat J Muhamedrahimov
This study examined the effect of a social-emotional intervention implemented in one St. Petersburg (Russian Federation) institution (called a Baby Home, BH) on the general behavioral development of preterm children (gestational ages of 30-36 weeks) during their first two years of life. The intervention consisted of training caregivers and implementing structural changes to create a more family-like environment. The study included preterm (N = 56) and full-term (N = 93) children from one BH that implemented the intervention and from another BH with no intervention...
January 2018: Infants and Young Children
Sylvain Fauquenoy, Valerie Migeot, Olivier Finet, Carlo Yague-Sanz, Olga Khorosjutina, Karl Ekwall, Damien Hermand
The cell fate decision leading to gametogenesis requires the convergence of multiple signals on the promoter of a master regulator. In fission yeast, starvation-induced signaling leads to the transcriptional induction of the ste11 gene, which encodes the central inducer of mating and gametogenesis, known as sporulation. We find that the long intergenic non-coding (linc) RNA rse1 is transcribed divergently upstream of the ste11 gene. During vegetative growth, rse1 directly recruits a Mug187-Lid2-Set1 complex that mediates cis repression at the ste11 promoter through SET3C-dependent histone deacetylation...
January 18, 2018: Current Biology: CB
Yixia Zhao, Fengqi Cao, Xiaohua Yu, Chuyan Chen, Jiao Meng, Ran Zhong, Yong Zhang, Dahai Zhu
Myogenic differentiation of skeletal muscle stem cells, also known satellite cells, is tightly orchestrated by extrinsic and intrinsic regulators. Basic fibroblast growth factor (FGF2) is well documented to be implicated in satellite cell self-renewal and differentiation by repressing MyoD. We recently identified a MyoD-regulated and skeletal muscle-specifically expressed long non-coding RNA Linc-RAM which enhances myogenic differentiation by facilitating MyoD/Baf60c/Brg1 complex assembly. Herein, we investigated the transcriptional regulation and intracellular signaling pathway in mediating Linc-RAM gene expression during muscle cell differentiation...
January 24, 2018: RNA Biology
Yansen Li, Zhanlong Shen, Bo Wang, Chunxiang Ye, Zhiyong Lai, Hongpeng Jiang, Zhu Wang, Kewei Jiang, Yingjiang Ye, Shan Wang
Increasing evidence has shown that abnormal expression of lncRNAs is involved in various biological behaviors and major cellular pathways of human cancers. However, the role of lncRNAs in the progression of gastric cancer has not been adequately investigated. Therefore, in this study, we investigated the expression levels of linc-GPR65-1 using Quantitative real-time PCR (qRT-PCR) and found that linc-GPR65-1 was significantly up-regulated in 50 gastric cancer tissues compared to the corresponding normal tissues...
January 16, 2018: Cell Cycle
Edison Ong, Jiangan Xie, Zhaohui Ni, Qingping Liu, Sirarat Sarntivijai, Yu Lin, Daniel Cooper, Raymond Terryn, Vasileios Stathias, Caty Chung, Stephan Schürer, Yongqun He
BACKGROUND: Aiming to understand cellular responses to different perturbations, the NIH Common Fund Library of Integrated Network-based Cellular Signatures (LINCS) program involves many institutes and laboratories working on over a thousand cell lines. The community-based Cell Line Ontology (CLO) is selected as the default ontology for LINCS cell line representation and integration. RESULTS: CLO has consistently represented all 1097 LINCS cell lines and included information extracted from the LINCS Data Portal and ChEMBL...
December 21, 2017: BMC Bioinformatics
Zhiwei Ji, Bing Wang, Ke Yan, Ligang Dong, Guanmin Meng, Lei Shi
BACKGROUND: In recent years, the integration of 'omics' technologies, high performance computation, and mathematical modeling of biological processes marks that the systems biology has started to fundamentally impact the way of approaching drug discovery. The LINCS public data warehouse provides detailed information about cell responses with various genetic and environmental stressors. It can be greatly helpful in developing new drugs and therapeutics, as well as improving the situations of lacking effective drugs, drug resistance and relapse in cancer therapies, etc...
December 21, 2017: BMC Systems Biology
Kevin F Boehnke, Rebecca K Brewster, Brisa N Sánchez, Manuel Valdivieso, Alejandro Bussalleu, Magaly Guevara, Claudia Gonzales Saenz, Soledad Osorio Alva, Elena Gil, Chuanwu Xi
BACKGROUND: Helicobacter pylori is a gut bacterium that is the primary cause of gastric cancer. H. pylori infection has been consistently associated with lack of access to sanitation and clean drinking water. In this study, we conducted time-series sampling of drinking water in Lima, Peru, to examine trends of H. pylori contamination and other water characteristics. MATERIALS AND METHODS: Drinking water samples were collected from a single faucet in Lima's Lince district 5 days per week from June 2015 to May 2016, and pH, temperature, free available chlorine, and conductivity were measured...
January 8, 2018: Helicobacter
Natalie Filippov-Levy, Hallel Cohen-Schussheim, Claes G Tropé, Thea E Hetland Falkenthal, Yoav Smith, Ben Davidson, Reuven Reich
OBJECTIVE: To profile long non-coding RNA (lncRNA) expression at the various anatomic sites of high-grades serous carcinoma (HGSC) and in effusion-derived exosomes. METHODS: LncRNA profiling was performed on 60 HGSC specimens, including 10 ovarian tumors, 10 solid metastases and 10 malignant effusions, as well as exosomes from 30 effusion supernatants. Anatomic site-related expression of ESRG, Link-A, GAS5, MEG3, GATS, PVT1 H19, Linc-RoR, HOTAIR and MALAT1 was validated by quantitative PCR and assessed for clinical relevance in a series of 77 HGSC effusions, 40 ovarian carcinomas, 21 solid metastases and 42 supernatant exosomes...
March 2018: Gynecologic Oncology
Samarjit Jana, Jagannath Jana, Kartick Patra, Soma Mondal, Jyotsna Bhat, Arnab Sarkar, Pallabi Sengupta, Anindya Biswas, Meghomukta Mukherjee, Satya Prakash Tripathi, Rahul Gangwal, Joyita Hazra, Abhay T Sangamwar, Gopeswar Mukherjee, Shamee Bhattacharjee, Deba Prasad Mandal, Subhrangsu Chatterjee
Discovery of anti-metastatic drugs is of immense clinical significance as metastasis is responsible for 90% of all cancer deaths. Here we report the inhibitory effect of a bis schiff base (M2) on cancer cell migration and invasion in vitro and in vivo. M2 has shown good solubility and permeability across the intestinal cell wall and hence can be classified as BCS (Biopharmaceutical classification system) class I. Microarray studies identified a long non coding intergenic RNA, LINC00273 as a novel molecular target of M2...
December 15, 2017: Oncotarget
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