The cell nucleus. The cell cycle and cell division

El núcleo como parte de la célula responsable de las funciones de reproducción y del mantenimiento y transmisión de la información genética resulta clave su estudio dentro de la Biología Celular. Para entender su funcionamiento se explica su composición y estructura; de la misma manera que se explican los diferentes conceptos relacionados, como por ejemplo cromatina, cromosoma, nucleoplasma, etc. Dentro de la temática de la reproducción nos encontramos con el ciclo celular en sus diferentes fases y los dos tipos de división celular con sus implicaciones biológicas.The core as part of the cell responsible for the functions of reproduction and the maintenance and transmission of genetic information is key study in Cell Biology. To understand its operation composition and structure is explained; in the same way that different related concepts are explained, such as chromatin, chromosome, nucleoplasm, etc. Within the theme of the play we find the cell cycle in its different phases and two types of cell division with their biological implications

Specificity and disease in the ubiquitin system

Post-translational modification (PTM) of proteins by ubiquitination is an essential cellular regulatory process. Such regulation drives the cell cycle and cell division, signalling and secretory pathways, DNA replication and repair processes and protein quality control and degradation pathways. A huge range of ubiquitin signals can be generated depending on the specificity and catalytic activity of the enzymes required for attachment of ubiquitin to a given target. As a consequence of its importance to eukaryotic life, dysfunction in the ubiquitin system leads to many disease states, including cancers and neurodegeneration. This review takes a retrospective look at our progress in understanding the molecular mechanisms that govern the specificity of ubiquitin conjugation

Plant ascorbate influence on cell division, growth and seed production of Arabidopsis Thaliana

Ascorbate (AsA) also known as vitamin C is a key antioxidant in plants. AsA is a multifunctional molecule involved in plant growth and development, in addition, its level in the plant organs was related to the plant hormone levels, and also was associated to regulate the cell cycle and cell division.<br /

Live cell division dynamics monitoring in 3D large spheroid tumor models using light sheet microscopy

<p>Abstract</p> <p>Background</p> <p>Multicellular tumor spheroids are models of increasing interest for cancer and cell biology studies. They allow considering cellular interactions in exploring cell cycle and cell division mechanisms. However, 3D imaging of cell division in living spheroids is technically challenging and has never been reported.</p> <p>Results</p> <p>Here, we report a major breakthrough based on the engineering of multicellular tumor spheroids expressing an histone H2B fluorescent nuclear reporter protein, and specifically designed sample holders to monitor live cell division dynamics in 3D large spheroids using an home-made selective-plane illumination microscope.</p> <p>Conclusions</p> <p>As illustrated using the antimitotic drug, paclitaxel, this technological advance paves the way for studies of the dynamics of cell divion processes in 3D and more generally for the investigation of tumor cell population biology in integrated system as the spheroid model.</p

A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study

Background: A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention. Methods an design: There are two principal arms to this study: (i) a cross-sectional study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii) an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and precancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division. Discussion: This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function

What determines cell size?

AbstractFirst paragraph (this article has no abstract) For well over 100 years, cell biologists have been wondering what determines the size of cells. In modern times, we know all of the molecules that control the cell cycle and cell division, but we still do not understand how cell size is determined. To check whether modern cell biology has made any inroads on this age-old question, BMC Biology asked several heavyweights in the field to tell us how they think cell size is controlled, drawing on a range of different cell types. The essays in this collection address two related questions - why does cell size matter, and how do cells control it

Targeted therapy for breast cancer prevention.

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer

The SPF27 Homologue Num1 Connects Splicing and Kinesin 1-Dependent Cytoplasmic Trafficking in Ustilago maydis

The conserved NineTeen protein complex (NTC) is an integral subunit of the spliceosome and required for intron removal during pre-mRNA splicing. The complex associates with the spliceosome and participates in the regulation of conformational changes of core spliceosomal components, stabilizing RNA-RNA- as well as RNA-protein interactions. In addition, the NTC is involved in cell cycle checkpoint control, response to DNA damage, as well as formation and export of mRNP-particles. We have identified the Num1 protein as the homologue of SPF27, one of NTC core components, in the basidiomycetous fungus Ustilago maydis. Num1 is required for polarized growth of the fungal hyphae, and, in line with the described NTC functions, the num1 mutation affects the cell cycle and cell division. The num1 deletion influences splicing in U. maydis on a global scale, as RNA-Seq analysis revealed increased intron retention rates. Surprisingly, we identified in a screen for Num1 interacting proteins not only NTC core components as Prp19 and Cef1, but several proteins with putative functions during vesicle-mediated transport processes. Among others, Num1 interacts with the motor protein Kin1 in the cytoplasm. Similar phenotypes with respect to filamentous and polar growth, vacuolar morphology, as well as the motility of early endosomes corroborate the genetic interaction between Num1 and Kin1. Our data implicate a previously unidentified connection between a component of the splicing machinery and cytoplasmic transport processes. As the num1 deletion also affects cytoplasmic mRNA transport, the protein may constitute a novel functional interconnection between the two disparate processes of splicing and trafficking

MiR-218 as a multifunctional regulator of oncogenic processes in different solid tumors

MicroRNAs are highly conserved small non-coding regulatory RNAs that involve in post transcriptional regulating of gene expression during different cellular mechanisms. Aberration of miR-218 expression during tumorigenesis of different solid tumors has been reported by numerous studies. In current systematic review article, by using the terms “miR-218” and “cancer” we first searched for English language articles in the PubMed database, published from 1993 to April 2014. Then by a comprehensive review of related articles, we provided some new insights that highlight novel features and functions of miR-218 in initiation and progression of solid tumors. The majority of these studies propose a tumor suppressing role for miR-218 considering the fact that it is significantly down-regulated in tumor tissues compared with normal specimens. Despite accumulating body of evidence regarding tumor suppressor functions of miR-218 in solid tumors; more intensive reviewing about available miR-218 recent original studies and interpretation of existing data, revealed the multifunctional role of miR-218 in these kinds of malignancies by targeting different corresponding target genes. Take all together, MiR-218 targets different cellular processes in cancer cells and its expression pattern is in an important association with various states and features of tumors. It seems that miR-218 can increase the speed of cell cycle and cell division in lower sample grades and along with progression of cancer cells it's function changes to stabilization the cancer cells and not allowing them to invade. thats why it often shows up-regulation in lower grades and down-regulation in metastatic phase. Therefore, it seems of great importance to check samples stage, grade, lymph node metastasis status and other tumor features before evaluation of miR-218 as a prognostic or diagnostic biomarker. © 2016, Iranian Neurogenetics Society. All rights reserved

Mathematical modelling in systems biology : cell cycle regulation during leaf development in Arabidopsis

In this thesis, we studied a mathematical modelling approach of systems biology in plants. We have concentrated on two different issues related to the cell cycle and cell division (especially in the plant Arabidopsis). The first issue is that of the epidermal cell population in the Arabidopsis leaf and the second issue deals with gene networks which play an important role during the cell cycle. The chapters are grouped into four parts. In Part I, we described the cell cycle as the series of events that takes place in a cell leading to its division and duplication. We also stated the general objective of the study. We addressed the various aspects of the problems and the key factors that are assumed to influence or cause the problems. We provided a comprehensive mathematical framework in Part II to be used in the other chapters for the modelling, simulation and analysing purposes. Here we introduced and studied Michaelis-Menten kinetics (a model of enzyme kinetics) and the quasi-steady state assumption to reduce the complexity of the model. We also introduced two basic mathematical models for the growth of cell size in plants. In Part III, we considered two case studies related to the cell cycle and cell division in Arabidopsis. The first case study is the temporal control of epidermal cell divisions in the Arabidopsis leaf. The growth of plant organs is the result of two processes acting on the cellular level, namely cell division and cell expansion. The precise nature of the interaction between these two processes is still largely unknown as it is experimentally challenging to disentangle them. The lower epidermal tissue layer of the Arabidopsis leaf is composed of two cell types, puzzle shaped pavement cells and guard cells, which build the stomata. We determined the cell number and the individual cell areas separately for both cell types during development. To dissect the rules whereby different cell types divide and expand, the experimental data were fit into a computational model that describes all possible changes a cell can undergo from a given day to the next day. The model allows to calculate the probabilities for a precursor cell to become a guard or pavement cell, the maximum size at which it can divide into two pavement cells or two guard cells, the cell cycle duration and two different growth rates for two kinds of cells (pavement and guard cells) in one population. The second case study deals with the fact that atypical E2F activity restrains APC/CCCS52A2 function obligatory for endocycle onset. We have demonstrated that the atypical E2F transcription factor E2Fe/DEL1 controls the onset of the endocycle through a direct transcriptional control of APC/C activity. Because E2Fe/DEL1 represses the CCS52A2 promoter, we hypothesize that its level must drop below a critical threshold to allow sufficient accumulation of CCS52A2 during late S and G2 phase for cells to proceed from division to endoreduplication. We built a mathematical model to analyse the above hypothesis. The model is based on an ODE model used for the binding of ligands to proteins with the help of Hill functions. This mathematical model helps to understand mechanistically how decreasing E2Fe/DEL1 levels can account for the division-to-endoreduplication transition. Finally, in Part IV, we discussed some future work to extend the above research. We suggested several ideas to design new experiments and increase the value of the models. The term ”we” is used throughout the text to underline the fact that every single result of the author’s work as represented in the thesis was only possible because of the provision of experiments, equipment, materials and scientific input from others