中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Cells sense their environment and adapt to it by fine-tuning their transcriptome. Wired into this network of gene expression control are mechanisms to compensate for gene dosage. The increasing use of reverse genetics in zebrafish, and other model systems, has revealed profound differences between the phenotypes caused by genetic mutations and those caused by gene knockdowns at many loci, an observation previously reported in mouse and Arabidopsis. To identify the reasons underlying the phenotypic differences between mutants and knockdowns, we generated mutations in zebrafish egfl7, an endothelial extracellular matrix gene of therapeutic interest, as well as in vegfaa. Here we show that egfl7 mutants do not show any obvious phenotypes while animals injected with egfl7 morpholino (morphants) exhibit severe vascular defects. We further observe that egfl7 mutants are less sensitive than their wild-type siblings to Egfl7 knockdown, arguing against residual protein function in the mutants or significant off-target effects of the morpholinos when used at a moderate dose. Comparing egfl7 mutant and morphant proteomes and transcriptomes, we identify a set of proteins and genes that are upregulated in mutants but not in morphants. Among them are extracellular matrix genes that can rescue egfl7 morphants, indicating that they could be compensating for the loss of Egfl7 function in the phenotypically wild-type egfl7 mutants. Moreover, egfl7 CRISPR interference, which obstructs transcript elongation and causes severe vascular defects, does not cause the upregulation of these genes. Similarly, vegfaa mutants but not morphants show an upregulation of vegfab. Taken together, these data reveal the activation of a compensatory network to buffer against deleterious mutations, which was not observed after translational or transcriptional knockdown.

Genetic compensation induced by deleterious mutations but not gene knockdowns

https://wildlife.onlinelibrary.wiley.com/doi/pdf/10.2193/0022-541X%282006%2970%5B1816%3AOWTOIW%5D2.0.CO%3B2

Out With the Old, In With the New

As for the contents, it seems that this could be a useful introductory text and there are ideas which can be used with able mathematicians studying Further Mathematics or Oxbridge Entrance. Inside the front cover there is to be found a table of integrals and some power series expansions, unfortunately without any indication of their range of convergence. On page 2 a separable equation is solved and on page 32 the method is justified! Personally I do dA 1 not like — = — kA leading to — d\ = — kdt; I much prefer that it leads straight to dT A

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/AC826D664EA9261A0EF0D7DD0F72F268/S002555720015017Xa.pdf/div-class-title-span-class-italic-ordinary-and-partial-differential-equations-with-applications-span-by-r-p-gilbert-and-h-c-howard-pp-613-45-1990-isbn-0-13-639956-8-ellis-horwood-div.pdf

Ordinary and partial differential equations with applications , by R. P. Gilbert and H. C. Howard. Pp 613. £45. 1990. ISBN 0-13-639956-8 (Ellis Horwood)

http://ma.ecsdl.org/content/MA2006-02/8/455.full.pdf

Characterization of Expanded Graphite Gas Diffusion Layers

The multipotent cells comprising the vertebrate neural crest (NC) generate an astonishing array of derivatives, including neuronal, skeletal and adrenal components and pigment cells. Zebrafish possess three chromatophores lineages, melanophores, iridophores and xanthophores, which lend themselves to investigating the complex gene regulatory networks (GRNs) underlying fate segregation of NC progenitors. Although the core GRN governing melanophore specification has been previously established, those guiding iridophore and xanthophore development remain elusive. This study explores the iridophore specification GRN via a previously employed systems biology approach. Loss and gain of function experiments were used to derive a preliminary GRN (model A), mathematically modelled using a system of differential equations and computationally simulated to predict gene expression dynamics. Predictions were experimentally evaluated and testable hypotheses were derived to render simulations of the resulting model B consistent with experimental observations. Iterations of this process led to a more sophisticated model D, which accurately predicted observed expression dynamics. Firstly, mutant phenotypes identified the transcription factors Sox10, Tfec and Mitfa and the receptor tyrosine kinase, Ltk, as key players for model A. Regulatory interactions were derived by analysing the spatiotemporal gene expression patterns on wild-type and mutant embryos by in situ hybridisation. Data indicated a sox10-dependent tfec/ltk positive feedback loop driving iridophore specification. Cycles of mathematical modelling and experimentation revealed important regulatory features, such as sox10 maintenance throughout iridophore development and its cooperation with tfec to activate the differentiation gene, pnp4a. Candidate repressors of mitfa, a melanocyte-specific target of sox10, were investigated. Surprisingly, data presented challenge the reported role of Foxd3, an established mitfa repressor, in iridophores. This study established the core GRN guiding specification of the NC-derived iridophore lineage using systems biology. Presented results reveal previously unacknowledged molecular mechanisms underlying fate choice and demonstrate the value of integrating experimental and mathematical approaches when investigating GRNs.

Investigating gene regulatory networks underlying zebrafish pigment cell development

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Kleio Petratou

Author Tools

Chat about Author

Papers

Investigating gene regulatory networks underlying zebrafish pigment cell development