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https://www.readbyqxmd.com/read/29454259/the-cellular-mechanisms-and-consequences-of-centromere-drive
#1
REVIEW
Lisa E Kursel, Harmit S Malik
During female meiosis, only one of four meiotic products is retained in the egg. It was previously proposed that chromosomes might compete for inclusion in the egg via their centromere 'strength'. Recent findings have revealed the primary requirements for such 'centromere drive'. First, CDC42 signaling from the oocyte cortex renders the meiotic I spindle asymmetric. Second, 'stronger' centromeres preferentially detach from microtubules in cortical proximity, making them more likely to orient away from the cortex, and be included in the egg...
February 14, 2018: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29453798/melatonin-protects-against-defects-induced-by-deoxynivalenol-during-mouse-oocyte-maturation
#2
Mei Lan, Jun Han, Meng-Hao Pan, Xiang Wan, Zhen-Nan Pan, Shao-Chen Sun
Deoxynivalenol (DON) is one of the most prevalent Fusarium mycotoxins in feedstuff and food. DON causes detrimental effects on human and animal reproductive systems by inducing oxidative stress and apoptosis. While melatonin is a multifunctional endogenous hormone which plays crucial roles in the development of animal germ cells and embryos as a robust deoxidizer. In present study, we explored the effects of melatonin on the DON-exposure mouse oocytes. Our in vitro and in vivo results showed that DON adversely affected mouse oocyte maturation and early embryo cleavage, while melatonin administration ameliorated the toxic effects of DON...
February 17, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29453740/arrestins-structural-disorder-creates-rich-functionality
#3
REVIEW
Vsevolod V Gurevich, Eugenia V Gurevich, Vladimir N Uversky
Arrestins are soluble relatively small 44-46 kDa proteins that specifically bind hundreds of active phosphorylated GPCRs and dozens of non-receptor partners. There are binding partners that demonstrate preference for each of the known arrestin conformations: free, receptor-bound, and microtubule-bound. Recent evidence suggests that conformational flexibility in every functional state is the defining characteristic of arrestins. Flexibility, or plasticity, of proteins is often described as structural disorder, in contrast to the fixed conformational order observed in high-resolution crystal structures...
February 16, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29453575/regulation-of-blood-testis-barrier-btb-dynamics-role-of-actin-and-microtubule-based-cytoskeletons
#4
Qing Wen, Elizabeth I Tang, Nan Li, Dolores D Mruk, Will M Lee, Bruno Silvestrini, C Yan Cheng
The blood-testis barrier (BTB) is an important ultrastructure in the testis that supports meiosis and postmeiotic spermatid development since a delay in the establishment of a functional Sertoli cell barrier during postnatal development in rats or mice by 17-20 day postpartum (dpp) would lead to a delay of the first wave of meiosis. Furthermore, irreversible disruption of the BTB by toxicants also induces infertility in rodents. Herein, we summarize recent findings that BTB dynamics (i.e., disassembly, reassembly, and stabilization) are supported by the concerted efforts of the actin- and microtubule (MT)-based cytoskeletons...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29450503/the-mechanical-contribution-of-vimentin-to-cellular-stress-generation
#5
Inge A E W van Loosdregt, Giulia Weissenberger, Marc P F H L van Maris, Cees W J Oomens, Sandra Loerakker, Oscar Stassen, Carlijn V C Bouten
Contractile stress generation by adherent cells is largely determined by the interplay of forces within their cytoskeleton. It is known that actin stress fibers, connected to focal adhesions, provide contractile stress generation, while microtubules and intermediate filaments provide cells compressive stiffness. Recent studies have shown the importance of the interplay between stress fibers and the intermediate filament vimentin. Therefore, the effect of the interplay between the stress fibers and vimentin on stress generation was quantified in this study...
February 14, 2018: Journal of Biomechanical Engineering
https://www.readbyqxmd.com/read/29449678/cytoskeleton-stability-is-essential-for-the-integrity-of-the-cerebellum-and-its-motor-and-affective-related-behaviors
#6
Rodrigo Muñoz-Castañeda, David Díaz, Leticia Peris, Annie Andrieux, Christophe Bosc, José M Muñoz-Castañeda, Carsten Janke, José R Alonso, Marie-Jo Moutin, Eduardo Weruaga
The cerebellum plays a key role in motor tasks, but its involvement in cognition is still being considered. Although there is an association of different psychiatric and cognitive disorders with cerebellar impairments, the lack of time-course studies has hindered the understanding of the involvement of cerebellum in cognitive and non-motor functions. Such association was here studied using the Purkinje Cell Degeneration mutant mouse, a model of selective and progressive cerebellar degeneration that lacks the cytosolic carboxypeptidase 1 (CCP1)...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449551/mutations-in-cfap43-and-cfap44-cause-male-infertility-and-flagellum-defects-in-trypanosoma-and-human
#7
Charles Coutton, Alexandra S Vargas, Amir Amiri-Yekta, Zine-Eddine Kherraf, Selima Fourati Ben Mustapha, Pauline Le Tanno, Clémentine Wambergue-Legrand, Thomas Karaouzène, Guillaume Martinez, Serge Crouzy, Abbas Daneshipour, Seyedeh Hanieh Hosseini, Valérie Mitchell, Lazhar Halouani, Ouafi Marrakchi, Mounir Makni, Habib Latrous, Mahmoud Kharouf, Jean-François Deleuze, Anne Boland, Sylviane Hennebicq, Véronique Satre, Pierre-Simon Jouk, Nicolas Thierry-Mieg, Beatrice Conne, Denis Dacheux, Nicolas Landrein, Alain Schmitt, Laurence Stouvenel, Patrick Lorès, Elma El Khouri, Serge P Bottari, Julien Fauré, Jean-Philippe Wolf, Karin Pernet-Gallay, Jessica Escoffier, Hamid Gourabi, Derrick R Robinson, Serge Nef, Emmanuel Dulioust, Raoudha Zouari, Mélanie Bonhivers, Aminata Touré, Christophe Arnoult, Pierre F Ray
Spermatogenesis defects concern millions of men worldwide, yet the vast majority remains undiagnosed. Here we report men with primary infertility due to multiple morphological abnormalities of the sperm flagella with severe disorganization of the sperm axoneme, a microtubule-based structure highly conserved throughout evolution. Whole-exome sequencing was performed on 78 patients allowing the identification of 22 men with bi-allelic mutations in DNAH1 (n = 6), CFAP43 (n = 10), and CFAP44 (n = 6). CRISPR/Cas9 created homozygous CFAP43/44 male mice that were infertile and presented severe flagellar defects confirming the human genetic results...
February 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29448966/exosomes-taken-up-by-neurons-hijack-the-endosomal-pathway-to-spread-to-interconnected-neurons
#8
Juan Carlos Polanco, Chuanzhou Li, Nela Durisic, Robert Sullivan, Jürgen Götz
In Alzheimer disease and related disorders, the microtubule-associated protein tau aggregates and forms cytoplasmic lesions that impair neuronal physiology at many levels. In addition to affecting the host neuron, tau aggregates also spread to neighboring, recipient cells where the misfolded tau aggregates, in a manner similar to prions, actively corrupt the proper folding of soluble tau, and thereby impair cellular functions. One vehicle for the transmission of tau aggregates are secretory nanovesicles known as exosomes...
February 15, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29448469/regulating-positioning-and-orientation-of-mitotic-spindles-via-cell-size-and-shape
#9
Jingchen Li, Hongyuan Jiang
Proper location of the mitotic spindle is critical for chromosome segregation and the selection of the cell division plane. However, how mitotic spindles sense cell size and shape to regulate their own position and orientation is still largely unclear. To investigate this question systematically, we used a general model by considering chromosomes, microtubule dynamics, and forces of various molecular motors. Our results show that in cells of various sizes and shapes, spindles can always be centered and oriented along the long axis robustly in the absence of other specified mechanisms...
January 2018: Physical Review. E
https://www.readbyqxmd.com/read/29445221/remodeling-of-the-actin-spectrin-membrane-associated-periodic-skeleton-growth-cone-collapse-and-f-actin-decrease-during-axonal-degeneration
#10
Nicolas Unsain, Martin D Bordenave, Gaby F Martinez, Jalil Sami, Catalina von Bilderling, Federico M Barabas, Luciano A Masullo, Aaron D Johnstone, Philip A Barker, Bisbal Mariano, Fernando D Stefani, Alfredo O Cáceres
Axonal degeneration occurs in the developing nervous system for the appropriate establishment of mature circuits, and is also a hallmark of diverse neurodegenerative diseases. Despite recent interest in the field, little is known about the changes (and possible role) of the cytoskeleton during axonal degeneration. We studied the actin cytoskeleton in an in vitro model of developmental pruning induced by trophic factor withdrawal (TFW). We found that F-actin decrease and growth cone collapse (GCC) occur early after TFW; however, treatments that prevent axonal fragmentation failed to prevent GCC, suggesting independent pathways...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29445053/spiral2-stabilises-endoplasmic-microtubule-minus-ends-in-the-moss-physcomitrella-patens
#11
Shu Yao Leong, Moé Yamada, Naoki Yanagisawa, Gohta Goshima
Stabilisation of minus ends of microtubules (MTs) is critical for organising MT networks in land plant cells, in which all MTs are nucleated independent of centrosomes. Recently, Arabidopsis SPIRAL2 (SPR2) protein was shown to localise to plus and minus ends of cortical MTs, and increase stability of both ends. Here, we report molecular and functional characterisation of SPR2 of the basal land plant, the moss Physcomitrella patens. In protonemal cells of P. patens, where non-cortical, endoplasmic MT network is organised, we observed SPR2 at minus ends, but not plus ends, of endoplasmic MTs and likely also of phragmoplast MTs...
February 15, 2018: Cell Structure and Function
https://www.readbyqxmd.com/read/29440930/advances-in-the-treatment-of-soft-tissue-sarcoma-focus-on-eribulin
#12
REVIEW
Panagiotis Koliou, Vasilios Karavasilis, Maria Theochari, Seth M Pollack, Robin L Jones, Khin Thway
Eribulin mesylate is a synthetic derivative of halichondrin B isolated from a marine sponge. Its mechanism of action is through microtubule inhibition, which is different from that of taxanes. Eribulin has been approved for the treatment of metastatic breast cancer and more recently for non-operable or metastatic liposarcoma in patients who have received prior anthracycline chemotherapy. The major side effects of eribulin are bone marrow suppression including neutropenia, leukopenia, anemia, and fatigue/weakness, which can be well managed...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29440728/highly-variable-contractile-performance-correlates-with-myocyte-content-in-trabeculae-from-failing-human-hearts
#13
Michelle L Munro, Xin Shen, Marie Ward, Peter N Ruygrok, David J Crossman, Christian Soeller
Heart failure (HF) is defined by compromised contractile function and is associated with changes in excitation-contraction (EC) coupling and cardiomyocyte organisation. Tissue level changes often include fibrosis, while changes within cardiomyocytes often affect structures critical to EC coupling, including the ryanodine receptor (RyR), the associated protein junctophilin-2 (JPH2) and the transverse tubular system architecture. Using a novel approach, we aimed to directly correlate the influence of structural alterations with force development in ventricular trabeculae from failing human hearts...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29440567/cellular-and-molecular-mechanisms-of-centromere-drive
#14
Michael A Lampson, Ben E Black
The asymmetric outcome of female meiosis I, whereby an entire set of chromosomes are discarded into a polar body, presents an opportunity for selfish genetic elements to cheat the process and disproportionately segregate to the egg. Centromeres, the chromosomal loci that connect to spindle microtubules, could potentially act as selfish elements and "drive" in meiosis. We review the current understanding of the genetic and epigenetic contributions to centromere identity and describe recent progress in a powerful model system to study centromere drive in mice...
February 12, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29440297/mi130004-a-novel-antibody-drug-conjugate-combining-trastuzumab-with-a-molecule-of-marine-origin-shows-outstanding-in-vivo-activity-against-her2-expressing-tumors
#15
Pablo M Aviles, Juan Manuel Dominguez, María José Guillén-Navarro, Maria Jose Muñoz-Alonso, Cristina Mateo, Raquel Rodriguez-Acebes, Jose Manuel Molina-Guijarro, Andrés Francesch, Juan Fernando Martínez-Leal, Simon Munt, Carlos M Galmarini, Carmen Cuevas
In the search for novel payloads to design new antibody-drug conjugates (ADCs), marine compounds represent an interesting opportunity given their unique chemical features. PM050489 is a marine compound that binds β-tubulin at a new site and disrupts the microtubule network hence leading to mitotic aberrations and cell death. PM050489 has been conjugated to trastuzumab via Cys residues through a non-cleavable linker and the resulting ADC, named MI130004, has been studied. Analysis of MI130004 delivered data consistent with the presence of two molecules of PM050489 per antibody molecule, likely bound to both sides of the intermolecular disulfide bond connecting the antibody light and heavy chains...
February 13, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29439518/the-neuroprotective-effects-of-cinnamic-aldehyde-in-an-mptp-mouse-model-of-parkinson-s-disease
#16
Woom-Yee Bae, Jae-Sun Choi, Joo-Won Jeong
Cinnamic aldehyde (CA), a key flavor compound in cinnamon essential oil, has been identified as an anti-oxidant, anti-angiogenic, and anti-inflammatory material. Recently, the neuroprotective effects of CA have been reported in various neurodegenerative disorders, including Parkinson's disease (PD). In neurons, autophagy is tightly regulated, and consequently, the dysregulation of autophagy may induce neurodegenerative disorders. In the present study, we found that the selective dopaminergic neuronal death in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models was prevented by CA...
February 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29438904/actin-microtubule-septin-and-escrt-filament-remodeling-during-late-steps-of-cytokinesis
#17
REVIEW
Cyril Addi, Jian Bai, Arnaud Echard
Cytokinesis is the process by which a mother cell is physically cleaved into two daughter cells. In animal cells, cytokinesis begins with the contraction of a plasma membrane-associated actomyosin ring that is responsible for the ingression of a cleavage furrow. However, the post-furrowing steps of cytokinesis are less understood. Here, we highlight key recent findings that reveal a profound remodeling of several classes of cytoskeletal elements and cytoplasmic filaments (septins, microtubules, actin and ESCRT) in the late steps of cytokinesis...
February 10, 2018: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29438359/effects-of-17%C3%AE-estradiol-on-mitophagy-in-the-murine-mc3t3-e1-osteoblast-cell-line-is-mediated-via-g-protein-coupled-estrogen-receptor-and-the-erk1-2-signaling-pathway
#18
Xiaoqi Sun, Xuhao Yang, Yuyan Zhao, Yinan Li, Lei Guo
BACKGROUND Osteoporosis is associated with 17β-estradiol deficiency. The G protein-coupled receptor 30 (GPR30) is known to be an estrogen-responsive receptor, but its role in the degradation of mitochondria in osteoblasts by autophagy, or mitophagy, remains unclear. The aim of this in vitro study was to evaluate the effects of 17β-estradiol, GPR30, and its signaling pathway, on mitophagy in the murine MC3T3-E1 osteoblast cell line. MATERIAL AND METHODS In the murine MC3T3-E1 osteoblast cell line, cells were treated with 17β-estradiol, or G15, a selective GPR30 antagonist, or U0126, a mitogen-activated protein (MAP) kinase (ERK1/2) inhibitor, or with vehicle as control...
February 13, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29438303/cytoskeletons-in-the-closet-subversion-in-alphaherpesvirus-infections
#19
REVIEW
Christopher E Denes, Monica Miranda-Saksena, Anthony L Cunningham, Russell J Diefenbach
Actin filaments, microtubules and intermediate filaments form the cytoskeleton of vertebrate cells. Involved in maintaining cell integrity and structure, facilitating cargo and vesicle transport, remodelling surface structures and motility, the cytoskeleton is necessary for the successful life of a cell. Because of the broad range of functions these filaments are involved in, they are common targets for viral pathogens, including the alphaherpesviruses. Human-tropic alphaherpesviruses are prevalent pathogens carried by more than half of the world's population; comprising herpes simplex virus (types 1 and 2) and varicella-zoster virus, these viruses are characterised by their ability to establish latency in sensory neurons...
February 13, 2018: Viruses
https://www.readbyqxmd.com/read/29437244/epothilone-d-correct-drug-wrong-disease
#20
EDITORIAL
Yazi D Ke, Lars M Ittner
Changes to the neuronal cytoskeleton, and in particular to microtubules, have been implicated in a wide range of neurodegenerative diseases, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). As such, there are growing reports of microtubules-modulating drugs used to treat neurodegeneration in mice. For example, long-term treatment of a mutant tau transgenic mouse model of FTD and AD with low doses of the cancer drug Epothilone D (EpoD), a microtubule stabilizing compound, reduced cognitive deficits in young animals [1] and improved neuropathology in aged animals [2], without overt side effects...
February 13, 2018: Neuropathology and Applied Neurobiology
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