nanog

Study Shows How the Nanog Protein Promotes Growth of Head and Neck Cancer

A new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC–James) has identified a biochemical pathway in cancer stem cells that is essential for promoting head and neck cancer.

The study shows that a protein called Nanog, which is normally active in embryonic stem cells, promotes the growth of cancer stem cells in head and neck cancer. The findings provide information essential for designing novel targeted drugs that might improve the treatment of head and neck cancer.

Normally, Nanog helps healthy embryonic stem cells maintain their undifferentiated, uncommitted (i.e., pluripotent) state. But recent evidence suggests that Nanog promotes tumor growth by stimulating the proliferation of cancer stem cells.

“This study defines a signaling axis that is essential for head and neck cancer progression, and our findings show that this axis may be disrupted at three key steps,” says principal investigator Quintin Pan, PhD, associate professor of otolaryngology at the OSUCCC – James. “Targeted drugs that are designed to inhibit any or all of these three steps might greatly improve the treatment of head and neck cancer.”

The findings were published in a recent issue of the journal Oncogene.

Specifically, the study shows that an enzyme called “protein kinase C-epsilon” (PKCepsilon) adds energy-packing phosphate groups to the Nanog molecule. This phosphorylation of Nanog stabilizes and activates the molecule.

It also triggers a series of events: Two Nanog molecules bind together, and these are joined by a third “co-activating” molecule called p300. This molecular complex then binds to the promoter region of a gene called Bmi1, an event that increases the expression of the gene. This, in turn, stimulates proliferation of cancer stem cells.

“Our work shows that the PKCepsilon/Nanog/Bmi1 signaling axis is essential to promote head and neck cancer,” Pan says. “And it provides initial evidence that the development of inhibitors that block critical points in this axis might yield a potent collection of targeted anti-cancer therapeutics that could be valuable for the treatment of head and neck cancer.”

(Image: Gray’s Anatomy of the Human Body)

CHOOSE LIFE.
CHOOSE COFFEE.
CHOOSE BIG FUCKING ROUTERS.
CHOOSE CROSS CONNECTS. CHOOSE PEERING SESSIONS.
CHOOSE NO SLEEP NO TIME OFF AND NO FRIENDS.
CHOOSE FIBER CUTS AND DDOS MITIGATION.
CHOOSE REVERSE DNS. CHOOSE BGPMON.
CHOOSE OSPF. CHOOSE ISIS. CHOOSE HOT POCKETS AT 4AM.
CHOOSE NANOG. CHOOSE CACTI. CHOOSE SNMP.
CHOOSE THE INTERNET.
CHOOSE LIFE.
CHOOSE NOC.
—  Serra Boten (@serraboten)
Digicert Internet Security Scholorship Submission

For the future of Internet security, we must assume the technology must have mass acceptance.  We must assume the technology is complex enough to befuddle governments, hackers, or others who wish to find faults in it.  And, we must assume that the technology can scale to achieve mass acceptance and not become weaker as it expands its reach.  It is also safe to assume that the use of cloud services will become widely accepted and implemented for both the enterprise as well as the consumer.  Internet security entails more than application level security such as SSL.  It is the total of the routers, switches, transmission lines, exchange points, firewalls, load balancers, etc.  There are so many attack vectors, Internet security must be carefully layered and orchestrated to provide multiple levels of protection.  This orchestration of layering is the direction the Internet must go to provide adequate security.  Internet Security must be an orchestration of security systems implemented at every level of the system and cooperatively managed by the providers of each service because cooperation is the only way to ensure a secure seamless handoff of data between service providers.

Communities like NANOG may offer an example of how an orchestrated security system would work.  It is an example of a community that has survived over 15 years, it is a successful example of a group of operators from across the world from all walks of network operations working together for a common good.  Indeed, the network is at the base layer of the system, and operational agreement on how security would be implemented at this layer would require parties to agree on standards.  Thankfully, at this level, security is relatively easy to gain adoption as each link could use a different security technology.  For example, as long as two parties agree on the technology, a given link could be encrypted using such technologies as Cisco’s link-level encryption found in their Nexus 7k series.

Moving up the stack, we could see improvements in technologies such as IPSEC/GRE and MPLS.  Although fundamentally different, they achieve similar goals.  These technologies are used to create tunnels through existing IP networks.  Unfortunately, the widely used MPLS technology doesn’t support native encryption and relies on security by layering IPSEC/GRE or other forms of encryption within the tunnel.  Even if one were to abandon MPLS, we need to look at the available accepted encryption standards and improve upon their strengths.  The same could be said for any encryption we talk about – it needs continue to be stronger and utilize the faster CPU and silicon that is available.  In any case, the import of orchestration between providers becomes greater than at the network layer.  The potential of providers needing to rely on globally accepted protocols and standards becomes greater as we move closer to the presentation layer.

Skipping up to the systems we build in the data center, we have a strong push into virtualization, SDN/ACI, and ultimately the Software Defined System/Infrastructure.  This SDI is where I think the final layer of infrastructure security will be realized.  If a set of SDI standards can be agreed upon, service providers can begin to integrate and include their security systems.  With the inclusion of security within the Software Defined domain, we can begin to imagine how a GSOG (Global Security Operators Group) could truly be effective.  We would begin to see how the layering effect of security would provide redundancy against multifaceted attacks and security failures, and longevity of security protocols such as SSL would increased with simple upgrades to things like encryption standards.

Pfft, what are you, stupid or lazy?

I asked in a networking channel once if there was a web interface for configuring cricket. I got preached at that it was easy and I should just write it myself. So I offered $3000 for anyone in the room to write it for me. Then I got crap for being “cheap”.

If its easy, how is that cheap?

There’s no end to the supply of people telling you how easy things are on the internet. They’ll usually even package it in the form of helpful advice like name-dropping a lot of related components. They’ll even derail into arguments about the pros and cons of other components. Yet nobody ever ponies up and names their price. Geeks have this fundamental disconnect in their brain that says “if I can concieve of how it could be done, everything after that is easy.” No, everything after that is work, and if our work was easy we wouldn’t be payed much more than a McJob would we?

Data Center Networking @ Facebook by David Swafford

I’ve been looking into data center fabrics and how you handle the scale of large networks lately so I decided I should take some time today to fully view the presentation(video and PDF) by David Swafford which he did at NANOG 59 late last year.

I met David Swafford when Facebook came to town for MPLS 2013. He was a really cool guy. I was inspired even at the time by hearing the way that they are going about support their networks. Very smart!

I took away a lot of nuggets from watching it. Here are a few:

  • Assume we can’t trust any rack
  • We can’t trust networking boxes either
  • Backbone devices are powerful in the wrong ways for a data center. They can handle many routes but don’t have the desired port density.
  • Going from 2 large leaf switches to many smaller leaf switches allows you to move from 1+1 to N+1.
  • Beware of silent failures by complex networking devices. They are hard to detect, BTW.
  • Automating ToR switch upgrades and handing a “push-button” interface to the service owners helped to remove the roadblocks for full upgrades of ToR switches. (I found it analogous to app upgrades on my phone)
  • They even scripted many parts of the process, such as determining who the on-call is for a given group at a given time. Fascinating.

Monitor all the things:

  • interface statistics and state
  • bgp statistics and state
  • FIBs
  • TCP retransmits

Respond to your Alerts with Automation:

  • FBAR stands for Facebook Automation Remediation
  • Receive Alert, login to device, verify still down, either ignore or remedy.

He also covers a lot of thoughts on engineers that automate:

  • Spend less time doing repetitive tasks
  • Spend more time solving interesting problems or learning

His final challenge: What would you do if you weren’t afraid?

『[*] I won’t be at the October meeting. My fiancee has made it clear
that a NANOG and ARIN honeymoon is not on her top 10 list, and
declined a suggestion that we submit our wedding vows to the ARIN AC
on a policy template.』
— 

NANOG Board Announcement

ウケた。そして某氏を思い出した。(だいぶ状況が違いそうだけど)

cellnews-blog.blogspot.se
Long-held Assumption of Gene Expression in Embryonic Stem Cells Challenged

A large body of research has reported that Nanog is allelically regulated — that is, only one copy of the gene is expressed at any given time — and fluctuations in its expression are responsible for the differences seen in individual embryonic stem (ES) cells’ predilection to differentiate into more specialized cells. These studies relied on cells that had a genetic marker or reporter inserted in the DNA upstream of the Nanog gene. This latest research suggests that results from studies based on this approach could be called into question.

Systemic delivery of human bone marrow embryonic-like stem cells improves motor function of severely affected dystrophin/utrophin-deficient mice.

PubMed:
Related Articles

Systemic delivery of human bone marrow embryonic-like stem cells improves motor function of severely affected dystrophin/utrophin-deficient mice.

Cytotherapy. 2014 Dec;16(12):1739-49

Authors: Pang RQ, He J, Zhang YY, Xiong F, Ruan GP, Zhu XQ, Wang Q, Wang JX, Zhu GX, Zhao J, Cai XM, Pan XH, Zhang C

Abstract
BACKGROUND AIMS: Embryonic-like stem cells (ELSCs) express embryonic stem cell-specific marker genes, such as SSEA-4, Oct-4 and Nanog, and can be induced to differentiate into cells of all 3 germ layers. Our preliminary data showed that ELSCs isolated from human bone marrow express multipotent antigen markers and differentiate into multinucleated myotube-like cells more efficiently than do mesenchymal stromal cells (MSCs) isolated from the same source. We investigated the therapeutic effect of ELSCs in dystrophin/utrophin double knock-out (dko) mice, one of the Duchenne muscular dystrophy animal models, by systemically transplanting them through tail-vein injection.
METHODS: ELSCs and MSCs were both isolated from human bone marrow. Two months after equal amounts of ELSCs or MSCs were injected through tail-vein injection, we evaluated skeletal muscle motor function and serum creatine kinase activity and measured dystrophin expression by means of immunostaining, Western blotting and semi-quantitative reverse transcriptase-polymerase chain reaction.
RESULTS: ELSCs positive for Oct-4 and Nanog-3 expressed higher levels of SSEA-4, FZD-9 and CD105 and were induced to differentiate into myotube-like cells more efficiently than did MSCs in vitro. Transplantation of ELSCs through the tail vein improved motor function and decreased serum creatine kinase activity at 2 months after cell transplantation. In addition, dystrophin protein and messenger RNA were upregulated and the skeletal muscle histology was improved in these dko mice transplanted with ELSCs.
CONCLUSIONS: ELSCs could be more efficiently induced to differentiate into myotubes than were MSCs in vitro, and systematically transplanting ELSCs improved muscle motor function and muscle histology in dko mice.

PMID: 25442501 [PubMed - indexed for MEDLINE] http://dlvr.it/BhwyQx

BMC Bioinformatics | Full text | Distribution Analyzer, a methodology for identifying and clustering outlier conditions from single-cell distributions, and its application to a Nanog report...

@rnomics/bioinfo biomedcentral.com - Ihor Lemischka 200) && (this.width >= this.height) ? 200: true); max-height: 200px; height: expression((this.height > 200) && (this.height >= this.width) ? 200: true); border: none;’/> Background: Chemical or small interfering (si) #RNA screens measure the effects of many independent experimental conditions, each applied to a population of cells (e.g., all of the cells in a well). High-content screens permit a readout (e.g., fluorescence, luminescence, cell morphology) from each cell in the population. Most analysis approaches compare the average effect on each population, precluding identification of outliers that affect the distribution of the reporter in the population but .  show all text posted by friends:  (1) @BioinformaticsP: BMC: Distribution Analyzer, a methodology for identifying and clustering outlier conditions from single-cell d… bit.ly/1VtUYbQ 22.07.2015 15.30.16 posted by followers of the list:  (0) http://bit.ly/1Om7zbH

Distribution Analyzer, a methodology for identifying and clustering outlier conditions from single-cell distributions, and its application to a Nanog reporter #RNAi screen

Background: Chemical or small interfering (si) #RNA screens measure the effects of many independent experimental conditions, each applied to a population of cells (e.g., all of the cells in a well). High-content screens permit a readout (e.g., fluorescence, luminescence, cell morphology) from each cell in the population. Most analysis approaches compare the average effect on each population, precluding identification of outliers that affect the distribution of the reporter in the population but not its average. Other approaches only measure changes to the distribution with a single parameter, precluding accurate distinction and clustering of interesting outlier distributions. Results: We describe a methodology to identify outlier conditions by considering the cell-level measurements from each condition as a sample of an underlying distribution. With appropriate selection of a distance metric, all effects can be embedded in a fixed-dimensionality Euclidean basis, facilitating identification and clustering of biologically interesting outliers. We demonstrate that measurement of distances with the Hellinger distance metric offers substantial computational efficiencies over alternative metrics. We validate this methodology using an #RNA interference (#RNAi) screen in mouse embryonic stem cells (ESC) with a Nanog reporter. The methodology clusters effects of multiple control si#RNAs into their true identities better than conventional approaches describing the median cell fluorescence or the commonly used Kolmogorov-Smirnov distance between the observed fluorescence distribution and the null distribution. It identifies outlier genes with effects on the reporter distribution that would have been missed by other methods. Among them, si#RNA targeting Chek1 leads to a wider Nanog reporter fluorescence distribution. Similarly, si#RNA targeting Med14 or Med27 leads to a narrower Nanog reporter fluorescence distribution. We confirm the roles of these three genes in regulating pluripotency by m#RNA expression and alkaline phosphatase staining using independent short hairpin (sh) #RNAs. Conclusions: Using our methodology, we describe each experimental condition by a probability distribution. Measuring distances between probability distributions permits a multivariate rather than univariate readout. Clustering points derived from these distances allows us to obtain greater biological insight than methods based solely on single parameters. We find several outliers from a mouse ESC #RNAi screen that we confirm to be pluripotency regulators. Many of these outliers would have been missed by other analysis methods. http://bit.ly/1Om7zbH #BMC

Distribution Analyzer, a methodology for identifying and clustering outlier conditions from single-cell distributions, and its application to a Nanog reporter #RNAi screen

Background: Chemical or small interfering (si) #RNA screens measure the effects of many independent experimental conditions, each applied to a population of cells (e.g., all of the cells in a well). High-content screens permit a readout (e.g., fluorescence, luminescence, cell morphology) from each cell in the population. Most analysis approaches compare the average effect on each population, precluding identification of outliers that affect the distribution of the reporter in the population but not its average. Other approaches only measure changes to the distribution with a single parameter, precluding accurate distinction and clustering of interesting outlier distributions. Results: We describe a methodology to identify outlier conditions by considering the cell-level measurements from each condition as a sample of an underlying distribution. With appropriate selection of a distance metric, all effects can be embedded in a fixed-dimensionality Euclidean basis, facilitating identification and clustering of biologically interesting outliers. We demonstrate that measurement of distances with the Hellinger distance metric offers substantial computational efficiencies over alternative metrics. We validate this methodology using an #RNA interference (#RNAi) screen in mouse embryonic stem cells (ESC) with a Nanog reporter. The methodology clusters effects of multiple control #siRNAs into their true identities better than conventional approaches describing the median cell fluorescence or the commonly used Kolmogorov-Smirnov distance between the observed fluorescence distribution and the null distribution. It identifies outlier genes with effects on the reporter distribution that would have been missed by other methods. Among them, #siRNA targeting Chek1 leads to a wider Nanog reporter fluorescence distribution. Similarly, #siRNA targeting Med14 or Med27 leads to a narrower Nanog reporter fluorescence distribution. We confirm the roles of these three genes in regulating pluripotency by #mRNA expression and alkaline phosphatase staining using independent short hairpin (sh) #RNAs. Conclusions: Using our methodology, we describe each experimental condition by a probability distribution. Measuring distances between probability distributions permits a multivariate rather than univariate readout. Clustering points derived from these distances allows us to obtain greater biological insight than methods based solely on single parameters. We find several outliers from a mouse ESC #RNAi screen that we confirm to be pluripotency regulators. Many of these outliers would have been missed by other analysis methods. http://bit.ly/1Om7zbH #BMC