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Patrick J Atkinson, Yaodong Dong, Shuping Gu, Wenwen Liu, Elvis Huarcaya Najarro, Tomokatsu Udagawa, Alan G Cheng
During development, Sox2 is indispensable for cell division and differentiation, yet its roles in regenerating tissues are less clear. Here, we used combinations of transgenic mouse models to reveal that Sox2 haploinsufficiency (Sox2haplo) increases rather than impairs cochlear regeneration in vivo. Sox2haplo cochleae had delayed terminal mitosis and ectopic sensory cells, yet normal auditory function. Sox2haplo amplified and expanded domains of damage-induced Atoh1+ transitional cell formation in neonatal cochlea...
March 19, 2018: Journal of Clinical Investigation
Emily Tubman, Yungui He, Thomas S Hays, David J Odde
Introduction: The microtubule motor protein kinesin-5 is well known to establish the bipolar spindle by outward sliding of antiparallel interpolar microtubules. In yeast, kinesin-5 also facilitates chromosome alignment "congression" at the spindle equator by preferentially depolymerizing long kinetochore microtubules (kMTs). The motor protein kinesin-8 has also been linked to chromosome congression. Therefore, we sought to determine whether kinesin-5 or kinesin-8 facilitates chromosome congression in insect spindles...
February 2018: Cellular and Molecular Bioengineering
Jinzhang Xiao, Qiuhong Wang, Qichang Yang, Hua Wang, Fulin Qiang, Song He, Jin Cai, Lei Yang, Yingying Wang
Gastric cancer is one of the most common types of malignancy worldwide. However, the molecular mechanisms of cancer development remain unclear. Src-associated in mitosis of 68 kDa (Sam68) is involved in cell proliferation, transformation, tumorigenesis and metastasis in several types of cancer. The present study aimed to assess the expression and function of Sam68 in human gastric cancer. Western blot analysis and immunohistochemistry indicated that Sam68 expression was increased in tumor samples and the levels were associated with the grade of malignancy...
April 2018: Oncology Letters
Xuepei Lei, Jianwei Jiao
Neural stem cell (NSC) proliferation and differentiation in the developing brain is a complex process precisely regulated by intrinsic and extrinsic signals. Although epigenetic modification has been reportedly involved in the regulation of the cerebral cortex, whether UTX, an H3K27me3 demethylase, regulates the development of cerebral cortex during the embryonic period is unclear. In this study, we demonstrate that Utx deficiency by knockdown and conditional knockout increases NSC proliferation and decreases terminal mitosis and neuronal differentiation...
March 9, 2018: Stem Cell Reports
Ningcheng Jiang, Minghai You, Yuhua Wang, Yide Huang, Shusen Xie, Yao Lin, Hongqin Yang
Mitosis is an important physiological event accompanying with dramatic changes of cellar biophysical properties. Failure of mitosis results in cell death or chromosome aneuploidy. In this study, we used atomic force microscopy to probe and compare the biophysical properties of tumor cells at different stages during mitosis. The rounding forces of MCF-7 cells oscillated during mitosis. At anaphase, the average elasticity of cells was higher than that at other phases. Cholesterol depletion with M[Formula: see text]CD led to an increase in the average elasticity, whereas the average roughness of membrane surface decreased at the absence of cholesterol...
March 17, 2018: Biomechanics and Modeling in Mechanobiology
Sara Villa-Hernández, Rodrigo Bermejo
Proliferating cells need to accurately duplicate and pass their genetic material on to daughter cells. Problems during replication and partition challenge the structural and numerical integrity of chromosomes. Diverse mechanisms, as the DNA replication checkpoint, survey the correct progression of replication and couple it with other cell cycle events to preserve genome integrity. The structural maintenance of chromosomes (SMC) cohesin complex primarily contributes to chromosome duplication by mediating the tethering of newly replicated sister chromatids, thus assisting their equal segregation in mitosis...
March 16, 2018: Current Genetics
Monika Raab, Mourad Sanhaji, Yves Matthess, Albrecht Hörlin, Ioana Lorenz, Christina Dötsch, Nils Habbe, Oliver Waidmann, Elisabeth Kurunci-Csacsko, Ron Firestein, Sven Becker, Klaus Strebhardt
The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities...
March 16, 2018: Nature Communications
Gamze Bildik, Nazli Akin, Filiz Senbabaoglu, Yashar Esmalian, Gizem Nur Sahin, Defne Urman, Sercin Karahuseyinoglu, Umit Ince, Erhan Palaoglu, Cagatay Taskiran, Macit Arvas, Yilmaz Guzel, Kayhan Yakin, Ozgur Oktem
Granulosa cell tumor of the ovary (GCT) is a very rare tumor, accounting for only 2% of all ovarian tumors. It originates from sex cords in the ovary and can be divided into adult (95%) and juvenile (5%) types based on histologic findings. To date, no clear etiologic process has been identified other than a missense point mutation in the FOXL2 gene. Our previous works showed that c-Jun N-terminal kinase (JNK) pathway plays critical role in cell cycle progression and mitosis of normal and immortalized granulosa cells and follicle growth in rodent ovaries...
March 16, 2018: Cell Death & Disease
Karolin Eifler, Sabine A G Cuijpers, Edwin Willemstein, Jonne A Raaijmakers, Dris El Atmioui, Huib Ovaa, René H Medema, Alfred C O Vertegaal
Signal transduction by small ubiquitin-like modifier (SUMO) regulates a myriad of nuclear processes. Here we report on the role of SUMO in mitosis in human cell lines. Knocking down the SUMO conjugation machinery results in a delay in mitosis and defects in mitotic chromosome separation. Searching for relevant SUMOylated proteins in mitosis, we identify the anaphase-promoting complex/cyclosome (APC/C), a master regulator of metaphase to anaphase transition. The APC4 subunit is the major SUMO target in the complex, containing SUMO acceptor lysines at positions 772 and 798...
March 16, 2018: Nature Communications
J Durgan, O Florey
Entosis is a form of epithelial cell engulfment and cannibalism prevalent in human cancer. Until recently, the only known trigger for entosis was loss of attachment to the extracellular matrix, as often occurs in the tumour microenvironment. However, two new studies now reveal that entosis can also occur among adherent epithelial cells, induced by mitosis or glucose starvation. Together, these findings point to the intriguing notion that certain hallmark properties of cancer cells, including anchorage independence, aberrant proliferation and metabolic stress, can converge on the induction of cell cannibalism, a phenomenon so frequently observed in tumours...
March 13, 2018: Biochimica et Biophysica Acta
Jennifer M Maurer, Charles G Sagerström
BACKGROUND: Signaling cascades, such as the extracellular signal-regulated kinase (ERK) pathway, play vital roles in early vertebrate development. Signals through these pathways are initiated by a growth factor or hormone, are transduced through a kinase cascade, and result in the expression of specific downstream genes that promote cellular proliferation, growth, or differentiation. Tight regulation of these signals is provided by positive or negative modulators at varying levels in the pathway, and is required for proper development and function...
March 15, 2018: BMC Developmental Biology
Nengquan Sheng, Li Yan, Kai Wu, Weiqiang You, Jianfeng Gong, Landian Hu, Gewen Tan, Hongqi Chen, Zhigang Wang
Colorectal cancer (CRC) is one of the most common neoplasms worldwide. However, the mechanisms underlying its development are still poorly understood. Thyroid hormone Receptor Interactor 13 (TRIP13) is a key mitosis regulator, and recent evidence has shown that it is an oncogene. Here, we report that TRIP13, which is overexpressed in CRC, is correlated with the CEA (carcino-embryonic antigen), CA19-9 (carbohydrate antigen 19-9) and pTNM (pathologic primary tumor, lymph nodes, distant metastasis) classification...
March 14, 2018: Cell Death & Disease
Mimi Gao, Melanie Berghaus, Simone Möbitz, Vitor Schuabb, Nelli Erwin, Marius Herzog, Karin Julius, Christian Sternemann, Roland Winter
For over 50 years, it has been known that the mitosis of eukaryotic cells is inhibited already at high hydrostatic pressure conditions of 30 MPa. This effect has been attributed to the disorganization of microtubules, the main component of the spindle apparatus. However, the structural details of the depolymerization and the origin of the pressure sensitivity have remained elusive. It has also been a puzzle how complex organisms could still successfully inhabit extreme high-pressure environments such as those encountered in the depth of oceans...
March 13, 2018: Biophysical Journal
Julia N Bailey, Laurence de Nijs, Dongsheng Bai, Toshimitsu Suzuki, Hiroyuki Miyamoto, Miyabi Tanaka, Christopher Patterson, Yu-Chen Lin, Marco T Medina, María E Alonso, José M Serratosa, Reyna M Durón, Viet H Nguyen, Jenny E Wight, Iris E Martínez-Juárez, Adriana Ochoa, Aurelio Jara-Prado, Laura Guilhoto, Yolly Molina, Elsa M Yacubian, Minerva López-Ruiz, Yushi Inoue, Sunao Kaneko, Shinichi Hirose, Makiko Osawa, Hirokazu Oguni, Shinji Fujimoto, Thierry M Grisar, John M Stern, Kazuhiro Yamakawa, Bernard Lakaye, Antonio V Delgado-Escueta
BACKGROUND: In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis. METHODS: Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase ( ICK)...
March 15, 2018: New England Journal of Medicine
Satoru Kudose, Masato Hoshi, Sanjay Jain, Joseph P Gaut
Acute kidney injury (AKI) is a significant cause of morbidity and mortality. Acute tubular injury is considered to be the early pathologic manifestation of AKI, however, the underlying pathology is complex, lacks standards for interpretation, and its relationship with AKI often is unclear or inconsistent. To clarify clinicopathologic correlations in AKI, we evaluated 32 histologic findings in 100 kidney biopsies from patients with AKI as a training set to correlate pathologic findings with clinical AKI grades...
March 13, 2018: American Journal of Surgical Pathology
Emad A Rakha, Mohamed Aleskandarani, Michael S Toss, Andrew R Green, Graham Ball, Ian O Ellis, Leslie W Dalton
AIMS: Virtual microscopy utilising digital whole slide imaging (WSI) is increasingly used in breast pathology. Histologic grade is one of the strongest prognostic factors in breast cancer (BC). This study aims at investigating the agreement between BC grading using traditional light microscopy (LM) and digital WSI with consideration of reproducibility and impact on outcome prediction. METHODS: A large (n=1675) well-characterised cohort of BC originally graded by LM was re-graded using WSI...
March 13, 2018: Journal of Clinical Pathology
Zay Yar Oo, Alexander J Stevenson, Martina A Proctor, Sheena M Daignault, Sebastian Walpole, Catherine Lanagan, Mu-Su Chen, Dubravka Skalamera, Loredana Spoerri, Stephen Ainger, Richard A Sturm, Nikolas K Haass, Brian Gabrielli
PURPOSE: CHEK1 inhibitors (CHEK1i) have single agent activity in vitro and in vivo. Here we have investigated the molecular basis of this activity. EXPERIMENTAL DESIGN: We have assessed a panel of melanoma cell lines for their sensitivity to the CHEK1i GNE-323 and GDC-0575 in vitro and in vivo. The effects of these compounds on responses to DNA replication stress were analyzed in the hypersensitive cell lines. RESULTS: A subset of melanoma cell lines are hypersensitive to CHEK1i-induced cell death in vitro, and the drug effectively inhibits tumour growth in vivo...
March 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yubo Xiao, Min Feng, Haiying Ran, Xiao Han, Xuegang Li
Increasing evidence has indicated that the abnormal expressions of certain genes serve important roles in tumorigenesis, progression and metastasis. The aim of the present study was to explore the key differentially expressed genes (DEGs) between non‑small cell lung cancer (NSCLC) and matched normal lung tissues by analyzing 4 different mRNA microarray datasets downloaded from the Gene Expression Omnibus (GEO) database. In improving the reliability of the bioinformatics analysis, the DEGs in each dataset that met the cut‑off criteria (adjust P‑value <0...
March 9, 2018: Molecular Medicine Reports
Arun Kumar, Priyanka Sharma, Mercè Gomar-Alba, Zhanna Shcheprova, Anne Daulny, Trinidad Sanmartín, Irene Matucci, Charlotta Funaya, Miguel Beato, Manuel Mendoza
The acquisition of cellular identity is coupled to changes in the nuclear periphery and nuclear pore complexes (NPCs). Whether and how these changes determine cell fate remain unclear. We have uncovered a mechanism that regulates NPC acetylation to direct cell fate after asymmetric division in budding yeast. The lysine deacetylase Hos3 associates specifically with daughter cell NPCs during mitosis to delay cell cycle entry (Start). Hos3-dependent deacetylation of nuclear basket and central channel nucleoporins establishes daughter-cell-specific nuclear accumulation of the transcriptional repressor Whi5 during anaphase and perinuclear silencing of the G1/S cyclin gene CLN2 in the following G1 phase...
March 12, 2018: Nature Cell Biology
Chao-Chieh Lin, Mayumi Kitagawa, Xiaohu Tang, Ming-Hsin Hou, Jianli Wu, Dan Chen Qu, Vinayaka Srinivas, Xiaojing Liu, J Will Thompson, Bernard Mathey-Prevot, Tso-Pang Yao, Sang Hyun Lee, Jen-Tsan Chi
The temporal activation of kinases and timely ubiquitin-mediated degradation is central to faithful mitosis. Here we present evidence that acetylation controlled by Coenzyme A synthase (COASY) and acetyltransferase CBP constitutes a novel mechanism that ensures faithful mitosis. We found that COASY knockdown triggers prolonged mitosis and multinucleation. Acetylome analysis reveals that COASY inactivation leads to hyper-acetylation of proteins associated with mitosis, including CBP and an Aurora A kinase activator, TPX2...
March 12, 2018: Nature Communications
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