Single-cell sequencing

Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell

grad students are very grad student-y

http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/2012_09_28/caredit.a1200108

2 American Scientists Win Nobel Prize in Chemistry

http://www.nytimes.com/2012/10/11/science/2-american-scientists-win-nobel-prize-in-chemistry.html?_r=0

The Biology of Belief

http://www.brucelipton.com/

By far, I don't agree with everything this guy says but some things do make you think outside the normal paradigm.

Vast F.D.A. Effort Tracked E-Mails of Its Scientists

http://www.nytimes.com/2012/07/15/us/fda-surveillance-of-scientists-spread-to-outside-critics.html?_r=1&nl=todaysheadlines&emc=edit_th_20120715

Washington Post Cover story on the job prospects of early career PhD Scientists

http://www.washingtonpost.com/national/health-science/us-pushes-for-more-scientists-but-the-jobs-arent-there/2012/07/07/gJQAZJpQUW_story_1.html

A few good nuggets:

"The lack of permanent jobs leaves many PhD scientists doing routine laboratory work in low-wage positions known as “post-docs,” or postdoctoral fellowships. Post-docs used to last a year or two, but now it’s not unusual to find scientists toiling away for six, seven, even 10 years. The post-doc system is “dysfunctional and not sustainable in the long term,” Princeton University President Shirley Tilghman told top brass at NIH in June."

“They’ll be employed in something,” said Michael S. Teitelbaum, a senior adviser to the Alfred P. Sloan Foundation who studies the scientific workforce. “But they go and do other things because they can’t find the position they spent their 20s preparing for.

A Movie of RNA Polymerase II Transcription

http://www.cell.com/abstract/S0092-8674%2812%2900697-6?utm_source=ECE001&utm_campaign=&utm_content=&utm_medium=email&bid=04V5L3F:ZFQBI1F#MainText

Can NIH Renovate the Biomedical Workforce?

http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/2012_06_22/caredit.a1200069

Have you ever thought about how TF find their binding sites?

Transcription factors (TFs) are proteins that regulate the expression of genes by binding sequence-specific sites on the chromosome. It has been proposed that to find these sites fast and accurately, TFs combine one-dimensional (1D) sliding on DNA with 3D diffusion in the cytoplasm. This facilitated diffusion mechanism has been demonstrated in vitro, but it has not been shown experimentally to be exploited in living cells. We have developed a single-molecule assay that allows us to investigate the sliding process in living bacteria. Here we show that the lac repressor slides 45 ± 10 base pairs on chromosomal DNA and that sliding can be obstructed by other DNA-bound proteins near the operator. Furthermore, the repressor frequently (>90%) slides over its natural lacO₁ operator several times before binding. This suggests a trade-off between rapid search on nonspecific sequences and fast binding at the specific sequence.

http://www.sciencemag.org/content/336/6088/1595.full

Why day dreaming makes you smarter and more creative?

If you see me staring at a paper for too long, would you please nudge me out of my daydream? Being almost a matchless daydreamer myself, I really do want to belive this article. But I completely disagree. Daydreaming is definitely not working its magic on me no matter what scientists like to believe. I am getting dumber by the day-quote n quote maryem hussein.
 http://www.newyorker.com/online/blogs/frontal-cortex/2012/06/the-virtues-of-daydreaming.html

Ever wondered how mosquitoes survive rain? Find out how...

http://www.csmonitor.com/Science/2012/0606/Why-don-t-mosquitoes-get-squashed-by-raindrops-Scientists-find-an-answer

Gene Expression by Remote Control

Radio-Wave Heating of Iron Oxide Nanoparticles Can Regulate Plasma Glucose in Mice

Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca²⁺-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells. 

grad school tumblr

http://whatshouldwecallgradschool.tumblr.com/

Re: How Your Cat Is Making You Crazy

http://translate.google.com/translate?sl=auto&tl=en&js=n&prev=_t&hl=en&ie=UTF-8&layout=2&eotf=1&u=http%3A%2F%2Fwww.calcalist.co.il%2Flocal%2Farticles%2F0%2C7340%2CL-3560740%2C00.html&act=url

-From Keren

How Your Cat Is Making You Crazy

Jaroslav Flegr is no kook. And yet, for years, he suspected his mind had been taken over by parasites that had invaded his brain. So the prolific biologist took his science-fiction hunch into the lab. What he’s now discovering will startle you. Could tiny organisms carried by house cats be creeping into our brains, causing everything from car wrecks to schizophrenia? 

http://www.theatlantic.com/magazine/archive/2012/03/how-your-cat-is-making-you-crazy/8873/?single_page=true

amazing letter to the editor

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2960341-9/fulltext

Lick your pups!

There is a really interactive site from U of Utah that explains a wide arrange of genetic concepts called Learn.Genetics (they have another for teachers/instructors called Teach.Genetics). One of their pages is on the epigenetics of the GR gene and you actually have to lick your pups before the time is up or else they will grow up having an impaired stress response. I thought this was neat.

http://learn.genetics.utah.edu/content/epigenetics/rats/

Sh*t Grad Students say...

A glimpse into our lives.  http://youtu.be/ovEghdXC4tE

Yamamoto was ahead of his time...

During the year I was born, Michael's old mentor published a review on steroid receptor regulation of gene networks (looking at all interesting angles of how these TF regulate gene expression).

Of course this piece below caught my eye....and it seems even more relevant today now that we have the technology to address genome wide studies. It may be less interesting since its steriod receptors but permissiveness and synergism may still apply to RXR. HERE's the complete paper.


Multifactor Regulation

Determinants of cell-specific gene networks can be viewed as static controls that are superimposed stably upon steroid RE function. In addition, there are dynamic controls that can have profound modulatory effects. Thus, hormone­ regulated genes are commonly controlled by multiple hormones and factors, and the characteristics of multifactor regulation are often more complex than those predicted by simple additivity of the effects of the individual regulators . Synergistic and permissive effects of two or more hormones upon the expres­ sion of single gene have been widely documented. For example, McKnight and coworkers (51; G. S. McKnight, personal communication) showed that es­ tradiol induction of ovalbumin transcription in oviduct tissue occurs only in the presence of insulin, while neither hormone alone is active. In some cases, permissive effects reflect the induction by one hormone of functional receptors for the second; thus, estradiol appears to permit progesterone and androgen induction of ovalbumin synthesis at least in part by inducing the appearance of progesterone and androgen receptors in oviduct cells (191). The permissive effect of insulin upon estrogen induction of ovalbumin differs, however, since transferrin induction by estradiol in the absence of insulin (51) shows that competent estrogen receptors are constitutively present.

A complementary pair of permissive effects has been described in rat HTC cells. In that system, cAMP alone fails to stimulate the expression of the tyrosine aminotransferase gene, but dexamethasone permits cAMP to act as a strong inducer (78); conversely, glucocorticoids have no effect on plasminogen activator mRNA production in HTC cells, whereas prior or simultaneous treatment with cAMP permits strong dexamethasone induction of plasminogen activator gene expression (68).

Little is known about the nature of permissive and synergistic effects of any two (or more) hormones. Posttranscriptional and/or posttranslational phe­ nomena (e.g. see 56) are likely to contribute in some cases to overall patterns of multifactor regulation, but these effects can also occur solely at the level of transcription. Such multifactor responses may reflect the differential activities of two or more distinct enhancers upon a single promoter under particular physiological conditions . To approach this notion experimentally, DeFranco et al (39; see also 225) constructed a simple recombinant plasmid into which two different enhancers could be inserted at positions where each could potentially act upon a specific promoter, itself inserted at a third position where it would lead to the production of an easily assayed "reporter" gene product; constructs bearing different enhancer and promoter combinations could then be trans­ fected into a variety of cell types. Using such plasmids containing an MTV GRE and a second heterologous enhancer, DeFranco et al discovered that the patterns of expression observed depended upon all three variables--enhancers , promoter, and cell type . Transfections in the presence or absence of glucocorti­ coids revealed that in certain combinations the paired enhancers stimulated promoter activity synergistically; in some cases activation of the GRE enhancer was required (i.e. "permissive") for function of an otherwise cryptic second enhancer.