Mystery at the heart of life

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December 21, 2014

Cell biology, Intelligent Design, News

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Cell biology
Intelligent Design
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By Biologic Institute’s Ann Gauger, at Christianity Today’s Behemoth, the secret life of cells:

Our bodies are made up of some 100 trillion cells. We tend to think of cells as static, because that’s how they were presented to us in textbooks. In fact, the cell is like the most antic, madcap, crowded (yet fantastically efficient) city you can picture. And at its heart lies a mystery—or I should say, several mysteries—involving three special kinds of molecules: DNA, RNA, and proteins.

These molecules are assembled into long chains called polymers, and are uniquely suited for the roles they play. More importantly, life absolutely depends upon them. We have to have DNA, RNA, and protein all present and active at the same time for a living organism to live.

How they work together so optimally and efficiently is not merely amazing, but also a great enigma, a mystery that lies at the heart of life itself. More. Paywall soon after. May be worth it.

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#409 follow-up? About 7 years after @409?
Pseudogenes: Pseudo-functional or key regulators in health and disease? Ryan Charles Pink, Kate Wicks, Daniel Paul Caley, Emma Kathleen Punch, Laura Jacobs and David Raul Francisco Carter doi: 10.1261/rna.2658311 RNA 2011. 17: 792-798 Pseudogenes have long been labeled as “junk” DNA, failed copies of genes that arise during the evolution of genomes. However, recent results are challenging this moniker; indeed, some pseudogenes appear to harbor the potential to regulate their protein-coding cousins. Far from being silent relics, many pseudogenes are transcribed into RNA, some exhibiting a tissue-specific pattern of activation. Pseudogene transcripts can be processed into short interfering RNAs that regulate coding genes through the RNAi pathway. In another remarkable discovery, it has been shown that pseudogenes are capable of regulating tumor suppressors and oncogenes by acting as microRNA decoys. The finding that pseudogenes are often deregulated during cancer progression warrants further investigation into the true extent of pseudogene function. In this review, we describe the ways in which pseudogenes exert their effect on coding genes and explore the role of pseudogenes in the increasingly complex web of noncoding RNA that contributes to normal cellular regulation. http://rnajournal.cshlp.org/content/17/5/792
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[Pseudogenes: structure conservation, expression, and functions]. Evgeniy Balakirev Francisco J Ayala Zhurnal obshche? biologii We describe some unexpected features of pseudogenes in diverse organisms that are inconsistent with this widely accepted point of view. Pseudogenes are often evolutionary conserved and transcriptionally active. Moreover, pseudogenes that have been suitably investigated often exhibit functional roles, such as gene regulation, generation of genetic diversity, and other features that are expected in genes or DNA sequences that have functional roles. A review of the evidence leads to the conclusion that pseudogenes are important components of genomes, representing a repertoire of sequences available for functional evolution and subject to non-neutral evolutionary changes. Pseudogenes might be considered as potogenes, i.e. DNA sequences with a potentiality for becoming new genes or acquire new functions. Furthermore we conjecture that some pseudogenes along with their parental sequences may constitute sets of indivisible functionally interacting entities (intergenic complexes or "intergenes"), in which all the component elements are required in order to fulfill a collective functional role. [Pseudogenes: structure conservation, expression, and functions]. - ResearchGate. Available from: http://www.researchgate.net/publication/8225600_Pseudogenes_structure_conservation_expression_and_functions
Over 10 years old paper.Dionisio_{May 13, 2015
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DNA methylation of the LIN28 pseudogene family Aaron P Davis, Abby D Benninghoff*, Aaron J Thomas, Benjamin R Sessions and Kenneth L White* BMC Genomics 2015, 16:287 doi:10.1186/s12864-015-1487-3 [...] little is known about how pseudogenes are targeted for methylation or how methylation levels are maintained in different tissues. Non-CpG methylation has been observed to occur with higher frequency in non-dividing cells and gametes, although its function remains unknown. [...] examination of more pseudogene families will be required to determine whether the same observation is consistent for other integrated pseudogenes Future [research] work should focus on these CpG sites and would further help determine how DNA methylation is targeted to specific genomic regions. [...] this observation does not rule out the possibility that CpG-rich pseudogenes could serve as sites for regulation of gene expression by methylation, a hypothesis that may also be addressed by survey of other pseudogene families. New knowledge on the regulation of pseudogenes via DNA methylation could contribute to greater understanding of the maintenance of global and/or regional patterns of methylation. Future work on this topic should focus on characterizing methylation patterns for other pseudogene families to determine whether all pseudogenes are maintained in a similar manner or whether sequence specific patterns can be identified through analysis of pseudogenes. http://www.biomedcentral.com/1471-2164/16/287
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DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns Kaie Lokk, Vijayachitra Modhukur, Balaji Rajashekar, Kaspar Märtens, Reedik Mägi, Raivo Kolde, Marina Koltšina, Torbjörn K Nilsson, Jaak Vilo, Andres Salumets* and Neeme Tõnisson* Genome Biology 2014, 15:r54 doi:10.1186/gb-2014-15-4-r54 This genome-wide methylation profiling study identified tissue-specific differentially methylated regions in 17 human somatic tissues. Many of the genes corresponding to these differentially methylated regions contribute to tissue-specific functions. Future studies may use these data as a reference to identify markers of perturbed differentiation and disease-related pathogenic mechanisms. hypomethylation, and not hypermethylation, was more likely to be associated with the tissue-specific functions. Our study also provoked the question, of how tDMRs mechanistically contribute to the tissue-specific functions, especially for the numerous methylation regions that were found in gene body areas. Still, it remains unclear, however, how the gene body tDMRs may function as regulators of gene expression, and this question should be addressed in the future epigenetic studies. http://genomebiology.com/2014/15/4/r54
http://link.springer.com/article/10.1186/gb-2014-15-4-r54/fulltext.html Work in progress... a few questions remain unanswered. Stay tuned.Dionisio_{May 13, 2015
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The human blood DNA methylome displays a highly distinctive profile compared with other somatic tissues Epigenetics Volume 10, Issue 4, 2015 DOI:10.1080/15592294.2014.1003744Robert Lowea*, Greg Slodkowiczb, Nick Goldmanb & Vardhman K Rakyana* pages 274-281 In mammals, DNA methylation profiles vary substantially between tissues. Recent genome-scale studies report that blood displays a highly distinctive methylomic profile from other somatic tissues. In this study, we sought to understand why blood DNA methylation state is so different to the one found in other tissues. We found that whole blood contains approximately twice as many tissue-specific differentially methylated positions (tDMPs) than any other somatic tissue examined. Furthermore, a large subset of blood tDMPs showed much lower levels of methylation than tDMPs for other tissues. Surprisingly, these regions of low methylation in blood show no difference regarding genomic location, genomic content, evolutionary rates, or histone marks when compared to other tDMPs. Our results reveal why blood displays a distinctive methylation profile relative to other somatic tissues. In the future, it will be important to study how these blood specific tDMPs are mechanistically involved in blood-specific functions. http://www.tandfonline.com/doi/abs/10.1080/15592294.2014.1003744?src=recsys
Interesting.Dionisio_{May 13, 2015
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Targeting the Stress Chaperome in Cancer: A Chemical Biology Approach [...] chaperones are expressed in all cells. They are one of the most abundant proteins. Therefore it has been really overlooked for many years until early ‘90s when serendipitous discovery of a small molecule has started what [...] http://www.worldpharmacongress.com/wpc_content.aspx?id=149478
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Back to the future: transgenerational transmission of xenobiotic-induced epigenetic remodeling Epigenetics Volume 10, Issue 4, 2015 DOI:10.1080/15592294.2015.1020267Josep C Jiménez-Chillaróna, Mark J Nijlandb, António A Ascensãoc, Vilma A Sardãod, José Magalhãesc, Michael J Hitchlere, Frederick E Domannf & Paulo J Oliveirad* pages 259-273 Epigenetics, or regulation of gene expression independent of DNA sequence, is the missing link between genotype and phenotype. Epigenetic memory, mediated by histone and DNA modifications, is controlled by a set of specialized enzymes, metabolite availability, and signaling pathways. A mostly unstudied subject is how sub-toxic exposure to several xenobiotics during specific developmental stages can alter the epigenome and contribute to the development of disease phenotypes later in life. Furthermore, it has been shown that exposure to low-dose xenobiotics can also result in further epigenetic remodeling in the germ line and contribute to increase disease risk in the next generation (multigenerational and transgenerational effects). We here offer a perspective on current but still incomplete knowledge of xenobiotic-induced epigenetic alterations, and their possible transgenerational transmission. We also propose several molecular mechanisms by which the epigenetic landscape may be altered by environmental xenobiotics and hypothesize how diet and physical activity may counteract epigenetic alterations. http://www.tandfonline.com/doi/full/10.1080/15592294.2015.1020267#.VVNVfpVFDIU
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In situ histone landscape of nephrogenesis DOI:10.4161/epi.26793 Epigenetic mechanisms have been implicated in impacting cell fate decisions during nephrogenesis; however, the chromatin landscape of nephron progenitors and daughter differentiating cells are largely unknown. We conclude that combinatorial histone signatures correlate with cell fate decisions during nephrogenesis. The present study examined the spatiotemporal distribution of histone modifications and modifiers during nephrogenesis. The potential significance of histone arginine methylation in nephrogenesis remains to be determined, since relatively little is known about the functions of these chromatin marks. The findings of the present study provide a general descriptive view of the histone landscape of the developing nephron but do not address other “epigenetic” marks such as DNA methylation and microRNA-based mechanisms. The data presented in this study are best interpreted within the context of functional data derived from existing and future ChIP-Seq data in nephron progenitors. In the future, it will be interesting to elucidate the effects of embryonic stressors on the epigenetic landscape of nephron progenitors in vivo. http://www.tandfonline.com/doi/full/10.4161/epi.26793
Work in progress... not there yet. A few* questions remain to be answered. (*) :)Dionisio_{May 13, 2015
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Repression of the soma-specific transcriptome by Polycomb-repressive complex 2 promotes male germ cell development doi: 10.1101/gad.246124.114 Genes Dev. 2014 Sep 15; 28(18): 2056–2069. Polycomb-repressive complex 2 (PRC2) catalyzes the methylation of histone H3 Lys27 (H3K27) and functions as a critical epigenetic regulator of both stem cell pluripotency and somatic differentiation, but its role in male germ cell development is unknown. Transcriptional profiling has revealed the dynamic changes to gene expression in differentiating germ cells, yet regulators of this program remain largely unidentified. PRC2 is a critical regulator of mammalian spermatogenesis, with essential roles in both the meiotic and mitotic compartments of the male germline. We hypothesize that* the ectopic expression of developmental genes in the absence of PRC2 compromises germ cell-specific transcription. PRC2 may control** spermatogonial maintenance through repression of developmental genes. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173155/
(*) look forward to reading newer papers confirming this hypothesis (**) look forward to reading newer papers changing this term "may control" to just "control(s)". Basically removing the word "may" so that the statement becomes a sure affirmation.Dionisio_{May 13, 2015
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PRC2 during vertebrate organogenesis: A complex in transición doi:10.1016/j.ydbio.2012.04.030 Recent years have witnessed tremendous progress in our understanding of the contribution of PRC2 to differentiation and cell fate specification, yet much remains to be explored. [...] remaining questions associated with its regulation and mechanisms of action. [...] the full spectrum of PRC2 alternative roles has not been explored. These studies highlight the need for a re-examination of the subcellular localization of PRC2 components, and for a proper dissection of its functional activities during the progression from proliferation to differentiation. http://www.sciencedirect.com/science/article/pii/S0012160612002199
This was 3 years ago... maybe these questions are answered now?Dionisio_{May 13, 2015
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Molecular Mechanisms of Podocyte Development Revealed by Zebrafish Kidney Research Miceli R, Kroeger PT, Wingert RA (2014) Molecular Mechanisms of Podocyte Development Revealed by Zebrafish Kidney Research. Cell Dev Biol 3:138. doi: 10.4172/2168-9296.1000138 there is still a rather limited understanding about the molecular pathways that control podocyte formation. In recent years, however, studies of podocyte development using the zebrafish embryonic kidney, or pronephros, have been an expanding area of nephrology research. These results suggest the ratio of these factors is important in the regulation of podocytes during development. Taken together, these biochemical studies reveal previously unknown physical interactions [...] different physical interactions of these proteins are capable of binding genomic targets, [...] switches in the complex components over time may orchestrate transcriptional alterations that proceed during podocyte differentiation. additional podocyte research with the zebrafish model is poised to make useful contributions to this area of nephrology in the years ahead. Continued work to identify Wt1 targets [34] and to ascertain the full transcriptional profile of podocytes [35,36], is necessary to solve the remaining enigmas of Wt1 function in podocyte ontogeny and identify players in podocyte gene regulatory networks, http://omicsgroup.org/journals/molecular-mechanisms-of-podocyte-development-revealed-by-zebrafish-kidney-research-2168-9296.1000138.php?aid=26675
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Post-transcriptional processing of genetic information and its relation to cancer (doi:10.3109/10520295.2012.730152) During the development, progression and dissemination of neoplastic lesions, cancer cells hijack normal pathways and mechanisms, especially those involved in repair and embryologic development. These pathways include those involved in intercellular communication, control of transcription, post-transcriptional regulation of protein production including translation of mRNAs, post-translational protein modifications, e.g., acetylation of proteins, and protein degradation. http://informahealthcare.com/doi/abs/10.3109/10520295.2012.730152 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091847/ doi: 10.3109/10520295.2012.730152
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Unraveling the mystery of cancer by secretory microRNA: horizontal microRNA transfer between living cells http://dx.doi.org/10.3389/fgene.2011.00097 the secretory mechanism and biological function, as well as the significance of extracellular miRNAs, remain largely unclear. not only exosomal miRNAs but also other types of secretory miRNAs could control the state of cellular phenotypes to the benefit of cancer cells within their niche. they have not provided evidence of the molecules species that take part in the modulation of the distal site of metastasis. To reveal the exact function of miRNA targeting sites that are distant from the primary organ, we should identify the molecular mechanisms of the tropism of secretory miRNA transported by carriers. The research field of secretory miRNAs has just begun. To use the knowledge of secretory miRNAs for human health, we should unveil the mystery of secretory RNA as follows. First, we need to know all the kinds of secretory RNA species. Second, secretory machinery of miRNAs and other types of RNA should be clarified. Last point is to know the function of secretory miRNAs in more detail, [...] Reports on the function of secretory miRNAs in physiological conditions, such as embryogenesis, organogenesis, and maintaining tissue and organ homeostasis, are not available*. Clarifying the species, mechanisms and roles of secretory miRNA, and other secretory ncRNAs in both pathological and physiological conditions would unveil the mystery of “secretory miRNAs-mediated disease” http://journal.frontiersin.org/article/10.3389/fgene.2011.00097/full
(*) 2012Dionisio_{May 12, 2015
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Nature presents multiple intriguing examples of processes which proceed at high precision and regularity. http://www.mathpubs.com/detail/1504.08116v1/Exploiting-stochastic-focusing-for-noise-reduction
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Binding of transcription factors adapts to resolve information-energy trade-off arXiv:1505.01215 [q-bio.GN] the binding of transcription factors to DNA in terms of an information transfer problem. The input of the noisy channel is the biophysical signal of a factor bound to a DNA site, and the output is a distribution of probable DNA sequences at this site. This task involves an inherent tradeoff between the information gain and the energetics of the binding interaction - high binding energies provide higher information gain but hinder the dynamics of the system as factors are bound too tightly. We show that adaptation of the binding interaction towards increasing information transfer under energy constraints implies that the information gain per specific binding energy at each base-pair is maximized. We analyze hundreds of prokaryote and eukaryote transcription factors from various organisms to evaluate the discrimination energies. We find that, in accordance with our theoretical argument, binding energies nearly maximize the information gain per energy. This work suggests the adaptation of information gain as a generic design principle of molecular recognition systems. http://arxiv.org/abs/1505.01215
design principle ?Dionisio_{May 11, 2015
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HOXA genes cluster: clinical implications of the smallest deletion Lidia Pezzani, Donatella Milani, Francesca Manzoni, Marco Baccarin, Rosamaria Silipigni, Silvana Guerneri and Susanna Esposito Italian Journal of Pediatrics 2015, 41:31 doi:10.1186/s13052-015-0137-3 http://www.ijponline.net/content/41/1/31 HOXA genes cluster plays a fundamental role in embryologic development. It is notable that in 2004 Lehoczky et al. demonstrated that EVX1, HIBADH, TAX1BP, JAZF1 and CREB5 show embryonic distal limb and genital bud expression, but at this time it is not known whether they have a role in their development. [10 years later still unknown?] In conclusion, this report improves our understanding of the genotype-phenotype correlations of HOXA genes cluster deletions via the identification and characterization of the smallest deletion (as well as critical region) reported to date, furthermore opening new discussion and interpretation cues on the unusual findings outlined.
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Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis doi: 10.1242/dev.110833 HOX proteins are a highly conserved family of transcription factors that play essential roles in defining axial identity during metazoan development. Hoxa3 has multiple complex and tissue-specific functions during patterning, differentiation and morphogenesis of the thymus and parathyroids. HOXA3 function is primarily restricted to early organogenesis [...] Hoxa3 regulates parathyroid differentiation and survival in a cell-autonomous manner it is unclear at this point how HOXA3 differentially affects the expression of a single gene in the dorsal versus ventral pouch the transcriptional initiator of the thymus program remains unknown. The identity of this pro-apoptotic signal is unclear – both SHH and inhibition of FGF signaling have been implicated in promoting this cell death; it is also unclear how these signaling pathways interact in this process although these signaling pathways might be involved in this aspect of the Hoxa3 mutant phenotype, the structure of the network that mediates this function has yet to be definitively identified. http://dev.biologists.org/content/141/19/3697.full
A few questions remain... stay tuned...Dionisio_{May 10, 2015
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The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells DOI: 10.3892/ijo.2015.2931 http://www.spandidos-publications.com/10.3892/ijo.2015.2931 Cranberry flavonoids (flavonols and flavan-3-ols), in addition to their antioxidant properties, have been shown to possess potential in vitro activity against several cancers. Overall, this study demonstrates promising in vitro cytotoxic and anti-proliferative properties of two newly characterized cranberry flavonoids, quercetin aglycone and PAC DP-9, against ovarian cancer cells.
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Non-histone protein methylation as a regulator of cellular signaling and function Nature Reviews Molecular Cell Biology 16, 5–17 (2015) doi:10.1038/nrm3915 Methylation of Lys and Arg residues on non-histone proteins has emerged as a prevalent post-translational modification and as an important regulator of cellular signal transduction mediated by the MAPK, WNT, BMP, Hippo and JAK–STAT signaling pathways. Crosstalk between methylation and other types of post-translational modifications, and between histone and non-histone protein methylation frequently occurs and affects cellular functions such as chromatin remodeling, gene transcription, protein synthesis, signal transduction and DNA repair. With recent advances in proteomic techniques, in particular mass spectrometry, the stage is now set to decode the methylproteome and define its functions in health and disease. http://www.nature.com/nrm/journal/v16/n1/full/nrm3915.html
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DNA double strand break repair pathway choice: A chromatin based decision? Nucleus Volume 6, Issue 2, 2015, Pages 107-113 DOI: 10.1080/19491034.2015.1010946 http://www.scopus.com/record/display.url?eid=2-s2.0-84928167800&origin=inward&txGid=F12A4FDD2C9C96291A6737DAB770DEDE.mw4ft95QGjz1tIFG9A1uw%3a2 DNA double-strand breaks (DSBs) are highly toxic lesions that can be rapidly repaired by 2 main pathways, namely Homologous Recombination (HR) and Non Homologous End Joining (NHEJ). The choice between these pathways is a critical, yet not completely understood, aspect of DSB repair. We recently found that distinct DSBs induced across the genome are not repaired by the same pathway. Indeed, DSBs induced in active genes, naturally enriched in the trimethyl form of histone H3 lysine 36 (H3K36me3), are channeled to repair by HR, in a manner depending on SETD2, the major H3K36 trimethyltransferase. Here, we propose that these findings may be generalized to other types of histone modifications and repair machineries thus defining a “DSB repair choice histone code”. This “decision making” function of preexisting chromatin structure in DSB repair could connect the repair pathway used to the type and function of the damaged region, not only contributing to genome stability but also to its diversity. © T Clouaire and G Legube.
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Non-histone protein methylation as a regulator of cellular signaling and function Nature Reviews Molecular Cell Biology 16, 5–17 (2015) doi:10.1038/nrm3915 http://www.nature.com/nrm/journal/v16/n1/full/nrm3915.html Methylation of Lys and Arg residues on non-histone proteins has emerged as a prevalent post-translational modification and as an important regulator of cellular signal transduction mediated by the MAPK, WNT, BMP, Hippo and JAK–STAT signaling pathways. Crosstalk between methylation and other types of post-translational modifications, and between histone and non-histone protein methylation frequently occurs and affects cellular functions such as chromatin remodeling, gene transcription, protein synthesis, signal transduction and DNA repair. With recent advances in proteomic techniques, in particular mass spectrometry, the stage is now set to decode the methylproteome and define its functions in health and disease.
Look forward, with much anticipation, to reading future research papers on this and related subjects, shedding more light on the elaborate cellular and molecular choreographies orchestrated within the biological systems. :)Dionisio_{May 10, 2015
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EGFR Modulates DNA Synthesis and Repair through Tyr Phosphorylation of Histone H4 doi:10.1016/j.devcel.2014.06.008 Posttranslational modifications of histones play fundamental roles in many biological functions. Specifically, histone H4-K20 methylation is critical for DNA synthesis and repair. However, little is known about how these functions are regulated by the upstream stimuli. These findings uncover a mechanism by which EGFR transduces signal to chromatin to regulate DNA synthesis and repair. http://www.sciencedirect.com/science/article/pii/S1534580714003797
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The Mysterious Ways of ErbB2/HER2 Trafficking doi:10.3390/membranes4030424 Among the receptors, ErbB2 is special in several ways. The reason(s) why ErbB2 is resistant to down-regulation are the subject of debate. The reason why ErbB2 is resistant to down-regulation remains unclear, and several discrepancies are reported. There can be many reasons for these discrepancies. It is suggested that multiple mechanisms collectively regulate endocytosis of the EGFR. This may also be the case for other receptors like ErbB2. A fascinating aspect is the suggestion that ErbB2 directly regulates the formation of coated pits. A conceptual question that remains is what role Hsp90 plays in inhibiting down-regulation of ErbB2. http://www.mdpi.com/2077-0375/4/3/424/htm
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Membrane and Integrative Nuclear Fibroblastic Growth Factor Receptor (FGFR) Regulation of FGF-23 doi: 10.1074/jbc.M114.609230 Fibroblastic growth factor receptor 1 (FGFR1) signaling pathways are implicated in the regulation of FGF-23 gene transcription, but the molecular pathways remain poorly defined. http://www.jbc.org/content/290/16/10447.abstract?related-urls=yes;290/16/10447
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The Role of Epigenetic Mechanisms in Notch Signaling During Development DOI: 10.1002/jcp.24851 The Notch pathway is a highly conserved cell–cell communication pathway in metazoan involved in numerous processes during embryogenesis, development, and adult organisms. Ligand-receptor interaction of Notch components on adjacent cells facilitates controlled sequential proteolytic cleavage resulting in the nuclear translocation of the intracellular domain of Notch (NICD). There it binds to the Notch effector protein RBP-J, displaces a corepressor complex and enables the induction of target genes by recruitment of coactivators in a cell-context dependent manner. Both, the gene-specific repression and the context dependent activation require an intense communication with the underlying chromatin of the regulatory regions. Since the epigenetic landscape determines the function of the genome, processes like cell fate decision, differentiation, and self-renewal depend on chromatin structure and its remodeling during development. In this review, structural features enabling the Notch pathway to read these epigenetic marks by proteins interacting with RBP-J/Notch will be discussed. Furthermore, mechanisms of the Notch pathway to write and erase chromatin marks like histone acetylation and methylation are depicted as well as ATP-dependent chromatin remodeling during the activation of target genes. An additional fine-tuning of transcriptional regulation upon Notch activation seems to be controlled by the commitment of miRNAs. Since cells within an organism have to react to environmental changes, and developmental and differentiation cues in a proper manner, different signaling pathways have to crosstalk to each other. The chromatin status may represent one major platform to integrate these different pathways including the canonical Notch signaling. J. Cell. Physiol. 230: 969–981, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company http://onlinelibrary.wiley.com/doi/10.1002/jcp.24851/abstract
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Nuclear FGF Receptor-1 and CREB Binding Protein: An Integrative Signaling Module DOI: 10.1002/jcp.24879 Whether nuclear FGFR1 targets these genes directly or only a subset of genes that initiate a cascade of downstream gene programs is under investigation. http://onlinelibrary.wiley.com/doi/10.1002/jcp.24879/full http://onlinelibrary.wiley.com/doi/10.1002/jcp.24879/epdf
The jury is still out... stay tuned... :)Dionisio_{May 9, 2015
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Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1) •DOI: 10.1371/journal.pone.0123380 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123380 Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development. Development of a multicellular organism from a single cell is regulated by myriads of TFs and requires the coordinated regulation of multi-gene programs. nFGFR1 has been proposed to act as a gate-opening factor in the feed-forward-and-gate module for control of CBP. Feed-forward loops are common in biological networks, serving as pulse generators, response-delaying circuits, signal-to-noise enhancers and signal integrators. nFGFR1-controlled feed-forward-and-gate loops are positioned at several strategic nodes that may increase the efficiency and reproducibility of ontogenic pathways.
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Dynamics of thymus organogenesis and colonization in early human development doi: 10.1242/dev.087320 The thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. The data presented above address the current profound gap in understanding of human thymus development. [...] it is also possible that other, as yet unknown mechanisms, limiting the time of onset of TEC differentiation are initiated or repressed with different kinetics to FOXN1 in the human. http://dev.biologists.org/content/140/9/2015.full
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Mechanisms of thymus organogenesis and morphogenesis doi: 10.1242/dev.059998 Understanding the developmental processes that build correct thymus structure is important because defects in thymus structure and function can result in serious health consequences, including immunodeficiency or autoimmunity. The details of the patterning and morphogenetic events are not fully understood and, therefore, not surprisingly, the molecular mechanisms regulating these tightly coordinated processes remain, for the most part, poorly defined. The existence and identity of this TEC stem cell, and whether it is present in both fetal and postnatal thymus, remains a topic of much debate and investigation in the field. [...] definitive functional data identifying the molecular mechanisms responsible for specification of thymus fate remain elusive. [...] there appears to be a `missing link' that establishes thymus fate [...] the links between the pathways and the transcription factors responsible for establishing initial thymus fate have still not been defined. We are now beginning to have a detailed picture of the events that occur during normal early thymus organogenesis and morphogenesis,[...] Perhaps the most glaring gap in our knowledge of thymus organogenesis is that we have not identified the molecular mechanisms responsible for specifying thymus, and parathyroid, fate. what signaling pathways and transcription factors do establish these organ fates? how early are organ fates specified? what is the cellular origin of the cervical thymus? Do the same mechanisms control thoracic and cervical thymus development and, if so, how are they induced and deployed at different times during development? how early and by what mechanisms are the cTEC and mTEC lineages established? What cellular processes (e.g. adhesion, migration) and specific pathways are required? http://dev.biologists.org/content/138/18/3865.full
Dionisio_{May 8, 2015
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Spatial-temporal model for silencing of the mitotic spindle assembly checkpoint Nature Communications 5, Article number: 4795 doi:10.1038/ncomms5795 Jing Chen & Jian Liu Previous models attribute the high sensitivity of SAC signaling to a biochemical bistable switch that arises from mutual inhibition between cyclin B, SAC proteins, and APC/C. However, recent findings indicate that reversible and irreversible SAC silencing processes coexist. This intriguing observation indicates that additional factors, not yet incorporated into existing models, are important for irreversible SAC silencing. experiments demonstrated extremely high precision of anaphase onset, which occurs only after the last kinetochore-spindle attachment becomes stable Future experimental findings can help improve the model with more realistic details, [...] A more realistic model requires future experiments [...] Future efforts will explore [...] How did the cell determine the spindle pole threshold signal? We do not have an answer, but we will use future experimental findings to develop more hypotheses. This model thus provided a unique solution to the robustness problem of SAC silencing in mitosis. It underscored the functional role of spatiotemporal regulation of SAC activity, and established a conceptual framework for understanding the mechanism that controls fidelity of mitosis. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163959/ http://www.nature.com/ncomms/2014/140912/ncomms5795/full/ncomms5795.html
Serious work. Interesting study material.Dionisio_{May 8, 2015
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