Student to research link between heart disease in women and secondhand smoke

Senior biochemistry major Tuyen Tran recently received a $3,000 research scholarship to aid him in his studies on how exposure to secondhand smoke may increase the risk of heart disease for women.

This research project will focus primarily on heart disease among women because, according to his statistical research papers, Tran explained that women tend to have a higher rate of heart disease than men.

Tran moved to the U.S. in 2004 from Vietnam with his family, and didn't speak any English at the time.

He began studying biology during his junior year at Golden West College, and transferred to Cal State Long Beach in 2009.

Tran's desire to become a researcher started at the age of 20, when his father died of cancer.

"I want to find the reason why we have the disease and the source of the reason," Tran said.

Tran's research will be conducted with the use of recombinant plasmid, a gene in vitro, from a rat to see how the smoke affects it.

Since a plasmid is a circular piece of DNA separated from chromosomal DNA that may be used in isolated "test tube" experiments, no live rodents will be used or harmed for Tran's research.

Tran said that he learned from his readings that secondhand smoke could expose people to the same conditions as primary smokers even though they aren't inhaling it directly.

"I think the reason why is because they inhale the smoke from many people, not just one cigarette," Tran said.

Tran explained that if someone walks across campus and passes several smokers, then they could be inhaling smoke from several different types of cigarettes.

He will conduct his research with his mentor Vasanthy Narayanaswami, assistant professor of biochemistry.

Tran has also received a lot of support from his family for his research.

"Sometimes I have to spend a lot of time at the lab, but they still understand and still support me," Tran said.

He said he wants to become a researcher and medical practitioner in pathology, the study and diagnosis of a disease.

He also said this project will give him the research experience necessary to be competitive for graduate school.

"I'm very excited and look forward to working on this project," Tran said. "I really want to find out why smoke relates to heart disease — it's very interesting."

Tran was one of only 11 students awarded the Howell-CSUPERB Research Scholar Award.

CSUPERB (CSU Program for Education and Research in Biotechnology) partnered with the Doris A. Howell Foundation for Women's Health Research to fund promising undergraduate student research projects in topics related to women's health.

 

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Student to research link between heart disease in women and secondhand smoke

Bite-Sized Biochemistry #47 – Transcription III / Translation I – Video

03-08-2011 14:15 Lecture by Kevin Ahern of Oregon State University discussing Biochemistry Basics in BB 451. See the full course at oregonstate.edu This course can be taken for credit (wherever you live) via OSU's ecampus. For details, see ecampus.oregonstate.edu Download Metabolic Melodies at http://www.davincipress.com Related courses include BB 350 - oregonstate.edu BB 450 - oregonstate.edu BB 100 - oregonstate.edu Transcription (continued) 1. A third modification to eukaryotic mRNAs that occurs is called editing. In editing, a base is chemically changed or added to an existing mRNA. Trypanosomes are unusual in inserting the base 'U' in multiple places in many mRNAs. Doing so is essential to getting the code right for making many of their proteins. 2. A more common editing modification that occurs in human cells is that involved with the Apo B-100 / Apo B-48 protein. Both proteins are coded by the same gene. (Note that I got the two proteins backwards in the lecture. What follows is correct) This lipoprotein is found in chylomicrons (Apo B-48) and liver cells (Apo B-100). Liver cells lack an RNA editing enzyme that intestinal cells have. The editing enzyme converts a C in a CAA sequence in the coding region of the gene to a U, making the stop codon UAA. 3. Splicing is the fourth modification that happens to eukaryotic mRNAs. Splicing also occurs to tRNAs and rRNAs in eukaryotes. Splicing involves removal of internal sequences from RNA followed by joining of ends. The removed sequences are ...

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Bite-Sized Biochemistry #47 - Transcription III / Translation I - Video

Bite-Sized Biochemistry #23 – Glycolysis III/Gluconeogenesis (Carbohydrate Metabolism) – Video

03-08-2011 12:09 (11/22/10) Lecture by Kevin Ahern of Oregon State University discussing Biochemistry Basics in BB 450. See the full course at oregonstate.edu This course can be taken for credit (wherever you live) via OSU's ecampus. For details, see ecampus.oregonstate.edu Download Metabolic Melodies at http://www.davincipress.com Related courses include BB 350 - oregonstate.edu BB 450 - oregonstate.edu BB 100 - oregonstate.edu Glycolysis II/III 1. Deficiency of the enzyme lactase leads to lactose intolerance 2. Regulation of glycolysis is controlled by three enzymes - hexokinase, PFK, and pyruvate kinase. Hexokinase's regulation is a bit complicated and is controlled partly by availability of substrate. 3. PFK is very unusual in being negatively regulated by a molecule (ATP) that is also a substrate. This is possible because the enzyme has an allosteric binding site for ATP in addition to the substrate binding site and the Km for the allosteric site is higher than the substrate binding site. 4. Pyruvate kinase is regulated both allosterically and by covalent modification (phosphorylation/dephosphorylation). Phosphorylation of the enzyme by a protein kinase turns the enzyme activity down, whereas F1,6BP acts as an allosteric activator. This activation is known as feedforward activation. 5. Feed forward activation is rare in metabolism. It is a term used to describe a metabolic product (such as F1,6BP above) that ACTIVATES an enzyme that catalyzes a reaction further ahead of it in a metabolic ...

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Bite-Sized Biochemistry #23 - Glycolysis III/Gluconeogenesis (Carbohydrate Metabolism) - Video

Teacher ratio condition for PG courses

Muzaffarpur, Feb. 16: Health minister Ashwini Kumar Choubey has said the state government was exploring the possibilities to start postgraduate courses in disciplines that have sufficient teacher strength at Sri Krishna Medical College and Hospital (SKMCH).

Choubey, who reviewed the ongoing health schemes with senior officials of Tirhut and Saran divisions last night, said the government was not averse to postgraduate courses, but SKMCH would be allowed to start courses in departments that have sufficient teachers.

In 2010, the Centre had allowed SKMCH to start postgraduate courses in 12 subjects. It provided Rs 6 crore to SKMCH for infrastructure development before introducing the postgraduate courses. But as things stand now, the heads of the departments of those courses, in which the postgraduate classes were scheduled to start, sat over the proposal allegedly to scuttle the move.

SKMCH principal D.K. Sinha had complained about the "lethargic approach" of the heads of various departments and sought immediate intervention of the government.

Choubey discussed the issue at length with the superintendent of SKMCH, G.K. Thakur, Sinha and other senior doctors. The minister said: "SKMCH would soon start postgraduate classes in medicine, surgery, preventive and social medicine, biochemistry, microbiology, pharmacology and pathology." The minister admitted that SKMCH was in a tight spot to start postgraduate courses for want of teachers. On the encephalitis breakout in Muzaffarpur and Gaya, the health minister said the state is leaving no stone unturned to control its surge and is prepared to prevent it.

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Why we're making a map of the brain

Allan Jones: A map of the brain

STORY HIGHLIGHTS

Allan Jones: We understand very little about how the brain works He says his organization is trying to unravel the secrets of this incredibly complex organ The institute is mapping activity in the human brain as a tool for researchers He says the work's practical benefits may include developing and understanding drugs

Editor's note: Allan Jones is chief executive of the Allen Institute for Brain Science. He holds a bachelor's of science in biology from Duke University and a Ph.D. in genetics and developmental biology from Washington University School of Medicine. He spoke at the TED Global conference in Edinburgh, Scotland, last year. TED is a nonprofit dedicated to "Ideas worth spreading," which it makes available through talks posted on its website.

(CNN) -- The brain is one of the last great frontiers of science. For all it does for us -- driving our thoughts, actions, perceptions and making us who we are -- we understand very little about how it works, its underlying biochemistry.

We know a fair amount about what parts of the brain are involved in particular functions from studies that track blood flow to reveal the locations of brain activity during certain behaviors or processes. We know that the back of the brain, the cerebellum, keeps us upright and is involved in coordinated movement.

We know that the sides of the brain, the temporal cortex, is involved in primary auditory processing, allowing us to hear words and send them into higher language processing centers. And we know the area toward the front of the brain is where complex thought and decision-making occur.

But taking a deeper look into the brain, beyond these broad areas of function, there is a great deal that is far less understood. The brain is incredibly complex, with about 86 billion nerve cells, called neurons, forming about 100 trillion connections, all working in concert to drive our thoughts, emotions, reactions and interactions with the world around us.

Each neuron is largely unique, driven by fundamental properties of its underlying biochemistry -- proteins controlling everything the nervous system has to do. All these proteins are encoded by our genome, comprising roughly 25,000 genes encoded in our DNA. The nature and activity of a given neuron is dictated by which of these 25,000 genes are turned on and to what level.

TED.com: A light switch for neurons

How does it all work? What are the roles of each neuron and how are they connected to our ultimate experience with the world? To answer these questions, we are seeking to understand which of our 25,000 genes are turned on in the brain, and where.

To this end, we have created a free online resource accessible to anyone, anywhere, anytime: the Allen Human Brain Atlas. The brain mapping process is complex and visually captivating, starting with a fresh, whole brain in the lab through to the molecular magnets that detect activity, or expression, of individual genes, and the subsequent informatics used to render this information into a meaningful piece of software that can be used to analyze the brain in more detail than we have ever had access to.

In 2006 we completed a map of the mouse brain. The mouse is the most common model for studying the mammalian brain, with the same basic parts and organization. The Allen Mouse Brain Atlas is used every day by thousands of scientists around the world. Creating this atlas put us in the unique position to tackle the challenges inherent in mapping the human brain.

Our laboratory receives fresh human brains that satisfy strict criteria -- no history of neurologic or psychiatric disease, no drug or alcohol abuse, and no brain damage occurring at death, among other criteria. We collect 3-D, MRI-based images of each whole brain to serve as a "scaffolding" from which we later map the gene expression information. Brains must be evaluated, imaged and frozen within 24 hours after death to preserve the signal we need to measure.

The brain is then sliced very thinly — 25 micrometers thick, thinner than a human hair — and sections are transferred to microscope slides, which are stained and analyzed for clusters and distributions of brain cells that provide a reference, kind of like a rough road map, to identify distinct regions in the brain.

TED.com: How to re-engineer a brain

We then take samples from each of these distinct regions (more than 1,000 of them), purify the RNA -- the signal indicating if a gene is turned on -- and obtain a readout of the level of activity of each gene for each area.

This method gives us roughly 50 million data points for each human brain. We put all that together into a single interactive database with meaningful search and visualization tools that are all freely available online at human.brain-map.org.

The goal is that this database will speed discovery, launching us into a new era of understanding of the human brain. Direct applications will be fruitful in areas like drug discovery, enhancing efficacy and reducing side effects of drugs for mental illness and disease. Further, we can start to connect the "what" to the "where" of gene expression in the brain, elucidating common pathways and beginning to unravel the mysteries of the inner workings of the brain's underlying biochemistry.

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The opinions expressed in this commentary are solely those of Allan Jones.

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Why we're making a map of the brain

Biochemistry professor receives patent

Posted: Wednesday, February 15, 2012 9:17 pm | Updated: 1:41 pm, Thu Feb 16, 2012.

One University professor is now teaching students with a new patent under his name.

Professor of biochemistry Dr. Rafiq Islam invented a method to detect sugar and silver nanoparticles by using a microwave.

According to the leading Life Science and high technology company, Sigma-Aldrich of St. Louis, silver nanoparticles are being incorporated into products that range from photovoltaic to biological and chemical sensors.

"I don't know how my invention will change people's lives," Islam admits. "But by simplifying procedure, it might be helpful for components they are making now."

Islam said he has been working on the invention since 2006. He believes it is an inexpensive task that other scientists and biochemists can use.

Although it took a few years to develop the invention, Islam said the process to receiving his patent was surprisingly simple.

Associate professor of organic chemistry at the University Dr. Ahmed Mlakawi watched Islam as he progressed with his soon-to-be patent. Mlakawi said a number of students have been asking him about Islam's newest invention.

"It's exciting and inspiring to those students who have been asking me about it," Mlakawi said.

Islam said he encourages students at the University to chase their dreams just like he did.

"We have a good number of resources in our department, and that should inspire them (students)," Islam said.

Islam is proud of his achievement, but said his invention won't stop with a patent.

Although his project is relatively new to him because it's in a field other than the one he specializes in, Islam enjoys the field of bioscience more.

"But I like to combine those two," Islam said. "I know I'm in biochemistry, but I want to try to move on and progress in nanochemistry as well."

Posted in News, Campus on Wednesday, February 15, 2012 9:17 pm. Updated: 1:41 pm.

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NSF Grant Challenges Traditional Teaching Strategies in Chemistry Labs

Newswise — Two South Dakota State University professors want to change the way students learn about chemistry. That’s the goal of a two-year, $200,000 National Science Foundation grant awarded to associate professors of chemistry and biochemistry, David Cartrette and Matt Miller.

“Students are typically given a recipe and don’t always think about how to change it to make a better experiment,” said Miller. “It’s just a verification process that we hope to change through introducing collaboration between first- and second-year chemistry students.”

The nationally funded laboratory curriculum the professors will write is built on three guiding principles. First, students need to be trained in lab techniques with scientific instruments used by most chemists in everyday work. Second, students need multiple opportunities to use these techniques and instruments to answer real-world questions related to science. Finally, experience shows students need to understand that successful, original research and experimentation is not a solo operation.

The lab teaching model developed by Miller and Cartrette brings together a hierarchical system of research that uses an apprentice/mentor model. Their teaching strategies mimic that model by having two different levels of undergraduate classes work together to create a community of learning much like faculty research that engages graduate students.

The interaction of the two class levels intends to simulate what happens when someone starts a new job. The newly hired person is typically trained by someone more experienced with the job and its responsibilities. The second-year students act as trainers, while the first-year students act as trainees. The goal of this interaction, said the professors, is to develop a team environment where students teach and learn from each other.

“The focus is on creativity and collaboration,” said Cartrette. “It’s taking the abstract and making it applicable to real world issues — taking knowledge and applying it to real world problems.”

Students in these lab courses begin their studies in a very traditional sense; they master the techniques used in a chemistry lab. As they progress through the curriculum, they use these techniques to address real problems for which no answer is known. The approach quickly moves students toward more independent thinking and motivates them to perform original experiments. Working collaboratively, the professors said, lets students experience what most research students experience as they begin the research process.

The professors said such cooperative environments help create greater interest in research as students learn about the social aspects of working with others, not unlike a professional research laboratory that includes a wide range of scientists.

Cartrette and Miller’s efforts address the call for science education enhancement at the state and national levels. In February 2012, President Obama received an executive report that recommended to “advocate and provide support for replacing standard laboratory courses with discovery based research courses.”

At the state level, the South Dakota Legislature is proposing increased funding for math and science teachers in public schools.

The NSF-funded curriculum model also addresses upcoming changes in medical school admissions procedures; future editions of the medical school admissions exam, or MCAT, will focus on performance outcomes, as opposed to factual knowledge recall. Miller and Cartrette’s project, funded last summer, they said, addresses these proposed changes.

“In a way, we foresaw these changes and acted to modify our curriculum to address them,” Cartrette said.

The NSF grant will fund the advanced instrumentation needed for the project. Associate Professor Kenneth Emo, from the Department of Teaching, Learning and Leadership, assisted by chemistry and biochemistry graduate student Jaclyn Nielsen, will evaluate the educational outcomes of the project.

Additionally, presentations made by Cartrette and Miller at national workshops will describe how students learn through collaborative interactions in a lab environment. The two will also write journal articles on the process and develop teacher-training workshops that can be replicated in other educational settings, at both universities and high schools.

Both Miller and Cartrette’s teaching experience has earned them awards for their instruction. Both have been awarded the Edward Patrick Hogan Award for Excellence in Teaching at SDSU to recognize outstanding achievement in undergraduate instruction. Miller has also received the Elaine and Leo Spinar Chemistry & Biochemistry Teaching Award from the Department of Chemistry and Biochemistry.

About South Dakota State University

Founded in 1881, South Dakota State University is the state’s Morrill Act land-grant institution as well as its largest, most comprehensive school of higher education. SDSU confers degrees from eight different colleges representing more than 175 majors, minors and specializations. The institution also offers 29 master’s degree programs, 12 Ph.D. and two professional programs.

The work of the university is carried out on a residential campus in Brookings, at sites in Sioux Falls, Pierre and Rapid City, and through Cooperative Extension offices and Agricultural Experiment Station research sites across the state.

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NSF Grant Challenges Traditional Teaching Strategies in Chemistry Labs

Plants that shut out bacterial invaders

I have a soft-spot for plant biology. In my final year at university, having exhausted all of the bacteria-related biochemistry lectures, I took a bacteria-related lecture course with the plants department. It was a smaller department, and seemed a lot friendlier and nicer. Also the biscuits in the tea-room were cheaper.

So I do like to write about plants every now and again, and it isn’t a very difficult task because like every other multicellular organism on the planet, plants also suffer from bacterial infections. Unlike humans, they don’t have a blood stream to carry immune cells around, so they instead rely on bombarding bacteria with nasty chemicals, quickly killing off any parts of the plant that get infected and acquiring a kind of plant resistance to stop attacks occurring again. (The three links are to a mini-series on plant immunology on my old blog.)

However in plants, as in humans, prevention is much better than cure and so the plant has all sorts of mechanisms to stop bacteria getting inside and causing infections in the first place. Plants have openings in their leaves called stomata which are used to control water levels inside the plant cells. The stomata open up to release moisture and close to retain it. They aren’t massive holes, but they can be seen with a light microscope and identified fairly easily by your average 16 year old (I remember looking at them during my AS levels!)

A stoma! The two curved things surrounding it are the two cells that control the opening. The small oval-shaped middle bit is the stoma - a hole in the cells covering the leaf. Image credit below.

As stomata are basically a hole from the inside of the plant to the great bacteria-ridden outdoors, it is important that they remain well-regulated. Plants can recognise bits of bacteria and when they do they can change internal conditions to close up the stomata, bolting the doors to prevent bacteria getting in. By sensing parts of bacteria such as (say) flagella, proteins are activated that change the concentrations of salts inside the cells surrounding the stomata, and cause them loose their curved shape and come together, effectively closing off the opening.

When plants were infected with the bacterial strain of Pseudomonas syringae the stomata closed up within 1-2 hours of infection, which for a plant is fairly rapid. However around 3-4 hours later the stomata started opening up again, and it wasn’t due to a bacterial protein, but a plant one. The protein in question was LecRK-V.5 and plants without the gene for this protein developed fewer disease symptoms and contained lower levels of internal bacteria than the non-mutated wild-types. The figure below shows the wild-type leaves at the top, with more disease symptoms than the healthier mutants below.

Figure from ref. 1

As stomatal opening is only one factor in the antibacterial plant response, the researchers then explored whether LecRK-V.5 was affecting any other responses. The main one being the production of dangerous Reactive Oxygen Species (ROS) which are often produced to damage invading bacteria. Both wild-type and LecRK-knockout-mutant plants showed no difference in levels of ROS, LecRK-V.5 only seems to affect the stomata.

The point about ROS also gives a clue as to just why the plant chooses to activate this protein following infection, seemingly making it easier for bacteria to gain access to the interior. In the mutant plant cells, with no LecRK-V.5, high levels of ROS started building up in the cells surrounding the stomata. ROS are dangerous to any cell they come into contact with, so by dampening down the response to bacterial infection around 4 hours following entry, the plant might be saving itself from being damaged by its own immune response. If the infection is still spreading after four hours, it may be more prudent for the plant to abandon the dead tissue and try and salvage what’s left. Leaves are not desperately important to plants after all, they can always grow more!

Ref 1:Desclos-Theveniau, M., Arnaud, D., Huang, T., Lin, G., Chen, W., Lin, Y., & Zimmerli, L. (2012). The Arabidopsis Lectin Receptor Kinase LecRK-V.5 Represses Stomatal Immunity Induced by Pseudomonas syringae pv. tomato DC3000 PLoS Pathogens, 8 (2) DOI: 10.1371/journal.ppat.1002513

Ref 2: Nicaise, V., Roux, M., & Zipfel, C. (2009). Recent Advances in PAMP-Triggered Immunity against Bacteria: Pattern Recognition Receptors Watch over and Raise the Alarm PLANT PHYSIOLOGY, 150 (4), 1638-1647 DOI: 10.1104/pp.109.139709

Credit for image 1.

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Plants that shut out bacterial invaders

GW researchers reveal digital transcriptome of breast cancer

Public release date: 14-Feb-2012
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Contact: Anne Banner
abanner@gwu.edu
202-994-2261
George Washington University Medical Center

GW Cancer Research Team in the Department of Biochemistry and Molecular Biology, in the School of Medicine and Health Sciences, published a study that is the first of its kind to use mRNA sequencing to look at the expression of genome, at a unprecedented resolution at the current time, in three types of breast cancer. The study titled, "Transcriptomic landscape of breast cancer through mRNA sequencing," is published in the Feb. 14 edition of the journal, Scientific Reports, a new open access Nature journal for large volume data.

Breast cancer is the leading cause of cancer death among women, accounting for about 23% of the total cancer cases and about 14% of the cancer deaths worldwide. One of current bottlenecks that hinder the translation of the current gene expression signatures for the benefits of patient is the highly heterogeneous nature of the disease. Therefore, one way to move forward is to identify and gain a deeper insight into the transcriptional regulatory machinery elements, which ultimately are responsible for phenotypic changes, for the next major leap in breast cancer genomic research and treatment. And this is exactly, what was done here, said the senior author and Team Leader Rakesh Kumar, Ph.D., of the project.

Using a sample set of 17 patients with three different types of breast cancer, the GW Research Team which also included collaborators from the John Hopkins College of Medicine and Baylor College of Medicine looked at similarities and differences in their gene expression patterns with a goal to identify biologically relevant, therapeutically important sets of targets in breast cancer. The researchers undertook a high throughput study to define comprehensive digital transcriptome and performed extensive comparative analysis of three groups of breast cancer from the total 1.2 billion reads at various levels of the transcriptional process. The comparative transcriptomic analyses illuminated common as well as differentially expressing transcripts between the three breast cancer groups. Further, high numbers of novel and unannotated transcripts, revealing global breast cancer transcriptomic adaptations in all three breast cancers were also identified.

"We are excited to be a part of this new approach to understand breast cancer. For the first time mRNA sequencing of human breast cancer tissues provides knowledge on central transcriptional regulatory elements, demonstrating the unexplored niches that could change the way breast cancer is previously understood," said lead author Jeyanthy Eswaran, PhD, Director of the McCormick Genomic and Proteomic Center in the department.

While most research today is mainly focused on preselected genes, GW's approach used a completely unbiased approach in order to come up with original snapshot of the breast cancer transcriptome. The GW researchers are working to gain a better understanding of the fundamental occurrences orchestrating the events that lead to a patient suffering from breast cancer. While searching for the highly abundant primary transcript groups which, the team identified osteonectin, guanine nucleotide binding protein beta polypeptide 2-like 1, calnexin calreticulin, ferritin L subunit, and beta-2 microglobulin (B2M) as the top five highly abundant primary transcript group in all three breast cancers. The GW research group is now teaming up with other breast cancer researchers to expend and validate some of the key findings of this work.

"From the on-going, follow-up work in the laboratory, it is clear that the significance of this study has implications beyond the current digital transcriptome of breast cancer as team is actively characterizing novel mutations in protein-coding genes and other elements of human genome that might be relevant in breast cancer," said Dr. Kumar. In addition, the work is likely to influence breast cancer genomics, the transcriptional regulation of cancer, and help built new biologic pathways in breast cancer in the coming years.

###

To view the paper in its entirety, visit: http://www.nature.com/srep/2012/120214/srep00264/full/srep00264.html

About the GW School of Medicine and Health Sciences:

Founded in 1825, the GW School of Medicine and Health Sciences (SMHS) was the first medical school in the nation's capital and is the 11th oldest in the country. Working together in our nation's capital, with integrity and resolve, the GW SMHS is committed to improving the health and well-being of our local, national and global communities. http://www.smhs.gwumc.edu


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GW researchers reveal digital transcriptome of breast cancer

Researchers reveal digital transcriptome of breast cancer

Breast cancer is the leading cause of cancer death among women, accounting for about 23% of the total cancer cases and about 14% of the cancer deaths worldwide. One of current bottlenecks that hinder the translation of the current gene expression signatures for the benefits of patient is the highly heterogeneous nature of the disease. Therefore, one way to move forward is to identify and gain a deeper insight into the transcriptional regulatory machinery elements, which ultimately are responsible for phenotypic changes, for the next major leap in breast cancer genomic research and treatment. And this is exactly, what was done here, said the senior author and Team Leader Rakesh Kumar, Ph.D., of the project.

Using a sample set of 17 patients with three different types of breast cancer, the GW Research Team which also included collaborators from the John Hopkins College of Medicine and Baylor College of Medicine looked at similarities and differences in their gene expression patterns with a goal to identify biologically relevant, therapeutically important sets of targets in breast cancer. The researchers undertook a high throughput study to define comprehensive digital transcriptome and performed extensive comparative analysis of three groups of breast cancer from the total 1.2 billion reads at various levels of the transcriptional process. The comparative transcriptomic analyses illuminated common as well as differentially expressing transcripts between the three breast cancer groups. Further, high numbers of novel and unannotated transcripts, revealing global breast cancer transcriptomic adaptations in all three breast cancers were also identified.

"We are excited to be a part of this new approach to understand breast cancer. For the first time mRNA sequencing of human breast cancer tissues provides knowledge on central transcriptional regulatory elements, demonstrating the unexplored niches that could change the way breast cancer is previously understood," said lead author Jeyanthy Eswaran, PhD, Director of the McCormick Genomic and Proteomic Center in the department.

While most research today is mainly focused on preselected genes, GW's approach used a completely unbiased approach in order to come up with original snapshot of the breast cancer transcriptome. The GW researchers are working to gain a better understanding of the fundamental occurrences orchestrating the events that lead to a patient suffering from breast cancer. While searching for the highly abundant primary transcript groups which, the team identified osteonectin, guanine nucleotide binding protein beta polypeptide 2-like 1, calnexin calreticulin, ferritin L subunit, and beta-2 microglobulin (B2M) as the top five highly abundant primary transcript group in all three breast cancers. The GW research group is now teaming up with other breast cancer researchers to expend and validate some of the key findings of this work.

"From the on-going, follow-up work in the laboratory, it is clear that the significance of this study has implications beyond the current digital transcriptome of breast cancer as team is actively characterizing novel mutations in protein-coding genes and other elements of human genome that might be relevant in breast cancer," said Dr. Kumar. In addition, the work is likely to influence breast cancer genomics, the transcriptional regulation of cancer, and help built new biologic pathways in breast cancer in the coming years.

More information: http://www.nature. … ep00264.html

Provided by George Washington University Medical Center

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Researchers reveal digital transcriptome of breast cancer

Planet of the Apes: As in 'Star Trek,' would aliens be similar to us?

On Star Trek, the aliens often look so human that crew members fall in love with them. But in real life, scientists in the field known as astrobiology can't be sure alien life would even be carbon-based like us, or use DNA to carry a genetic code.

Some insight now is coming from earthly labs, where scientists are building alternative kinds of genetic codes, and showing how they can evolve.

Whether life could be built with an alien biochemistry was among the more interesting questions that came up during a public event with famed biologist Richard Dawkins and physicist Lawrence Krauss, author of the book The Physics of Star Trek.

Dawkins saw the question as a biological equivalent of one posed by Einstein: Did God have any choice in making the universe? Not that Einstein believed in a biblical God, as the famously atheistic Dawkins was quick to point out.

Dawkins noted that 99 percent of the living things that ever existed are now extinct. The way carbon-based life works on Earth is downright wasteful, he said. "Any decent engineer would have sent it back to the shop."

The event, which drew more than 3,000 people, was held at Arizona State University in Tempe. Dawkins didn't lecture but instead took part in an onstage discussion with Krauss, who runs a multidisciplinary program there on the origins of humanity, life, and the cosmos.

Krauss - while not going so far as to say alien chicks would be hot - did say the laws of physics and chemistry might favor carbon-based life resembling ours.

Dawkins said he was inclined to think life could exist in more diverse forms, as long as it included some kind of code-carrying system equivalent to DNA, copying itself with high fidelity. Such genetic material is critical for Darwinian evolution, which, to Dawkins and many others, is the defining characteristic of life.

Perhaps it wasn't a complete coincidence that at the same university, biochemist John Chaput was creating an alternative version of DNA, called TNA, and had last month published the first evidence that the stuff can undergo Darwinian evolution.

Chaput, who works at ASU's Biodesign Institute, said Dawkins is correct to emphasize the need for genetic material - something that can carry a code. All known life does this with DNA and RNA.

NASA has taken a great interest in such possible alternative code-carriers. In late 2010 the space agency claimed that scientists had forced a bacteria to substitute arsenic for phosphorus in its DNA. Despite the fanfare, the team never presented adquate evidence that alternative life really existed, said chemist Steve Benner of the Florida-based Foundation for Applied Molecular Evolution.

And when biochemist Rosemary Redfield of the University of British Columbia tried to replicate this, she discovered that the bacteria failed to grow when fed arsenic and no phosphorus.

Benner said the original arsenic life paper admitted to a small amount of phosphorus contamination. From the start, he said, he thought the contamination was fooling the team into thinking the organism was using arsenic the way we use phosphorus.

Benner said this new TNA work is just as exciting and relevant to astrobiology as the arsenic bacteria would have been if it had been proved.

This alternative genetic material is like RNA in that it's single-stranded and it carries a chemical code with four different units. But the backbone that holds it together has a different structure, incorporating a sugar called threose where RNA has a sugar called ribose.

Threose is found in meteorites, said Chaput, suggesting it can form spontaneously in the absence of life. It's also simpler than RNA, making it a reasonable candidate for a precursor to our current genetic material.

The existence of a precursor fits with the widely held view that life didn't start out as complex as even the simplest microbes today. Instead, the simplest known living things evolved from yet simpler life that no longer exists.

Chaput showed that, like RNA, TNA can undergo Darwinian evolution. In theory, then, life elsewhere could use TNA as its genetic code, and if early life on Earth used it, TNA-based life could evolve into DNA-based life.

To demonstrate TNA evolution, he used selection to prompt the molecules to do a fairly simple task - to stick to a specific protein. This is what so-called receptors do in our bodies. He continued to select those TNA molecules that best stuck to the protein until he had a decent receptor.

TNA evolution worked the same way as in DNA, with accidental mutations leading to variation, and natural selection amplifying those variants that are best at surviving and reproducing themselves.

That suggests the possibility of TNA-based life elsewhere, said Benner. It's also possible, he said, that arsenic-using DNA would be stable, say, under the frigid conditions of Saturn's moon Titan.

So now we have TNA and code-carrying molecules that use six or 12 characters rather than the usual four. With these increasing possibilities known, Benner sides more closely with Dawkins on the question of life forms with alternative chemistries.

Our life is not the best of all possible forms, Benner said, but a product of chance, our biochemistry hinging on which molecules happened to bump into each other. God did have alternatives, in other words, but chance determined which one would evolve to create works like Star Trek.

 

Contact staff writer Faye Flam at 215-854-4977, fflam@phillynews.com, on her blog at http://www.philly.com/evolution, or @fayeflam on Twitter.

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Planet of the Apes: As in 'Star Trek,' would aliens be similar to us?

UCSB Researcher Team Develops Better Understanding of Leukemia Biology | The Daily Nexus

UCSB chemistry and biochemistry professor Norbert Reich and his team of researchers have recently discovered a molecular pathway that may explain the way acute myeloid leukemia develops.

AML is a cancer that occurs inside the bone marrow and destroys healthy blood cells. Eventually, patients become more susceptible to infections and prone to bleeding due to the decrease in the number of normal red and white blood cells as well as platelets.

According to Reich, a mutation in the protein DNMT3A affects the translation of DNA. DNMT3A encodes DNA methyltransferases — enzymes that catalyze the addition of a methyl group to the cytosine residues of CpG dinucleotides. This is the site where cytosine, one of the main bases found in DNA and RNA, can be methylated, or “tagged,” to turn on or off a certain gene. In AML patients, there is a mutation that disrupts the four proteins involved in tagging.

Reich’s research on DNA methyltransferases coincided with another group’s similar medical research regarding AML.

“It just happened to be that the enzyme we were studying applied to AML patients,” Reich said. “DNMT3A is not specific to just AML.”

Since it is involved in mammalian development, the mutations of DNMT3A are also applicable to other types of cancers. Overexpression of this protein has been reported in numerous studies on malignancies including prostate, colorectal and breast tumors.

The team’s research is based on the theory of epigenetics, the study of changes in gene activity that do not involve alterations in the genetic code but are still passed down to at least one successive generation. Every cell in the body has the same DNA yet differs in its epigenome, or tagging pattern. This difference allowed Reich to make the connection between the disrupted tagging pattern and its prevalence in leukemia patients. Upon observing this phenomenon, Reich proposed treating cancer using new methods rather than embracing the traditional “one-fits-all” chemotherapy.

Reich used rats to observe applied epigenetics and observed how a mother rat’s grooming and nursing methods could affect the long-term behavior of her offspring.

“We’ve all heard that the way your mother treats you when you’re younger shapes how you are when you’re older,” Reich said. “But this is the chemistry behind that phenomenon.”

These effects can be correlated with DNA methylation. Epigenetics may be seen as the convergence of the nature versus nurture theory.

“We’re talking about change within one generation,” Reich said. Epigenetics is based on the idea that environmental stressors can elicit a biological response that can be inherited through successive generations. If the environmental stressor is removed, however, the epigenetic marks will eventually fade and revert back to the original DNA programming.

Despite the potential this epigenetics research has for better cancer treatment, a final analysis of the research’s findings and their applicability has yet to be definitively determined.

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UCSB Researcher Team Develops Better Understanding of Leukemia Biology | The Daily Nexus

Good Timing: NIST/CU Collaboration Adds Timing Capability To Living Cell Sensors

Individual cells modified to act as sensors using fluorescence are already useful tools in biochemistry, but now they can add good timing to their resumé, thanks in part to expertise from the National Institute of Standards and Technology (NIST).

With the added capability to track the timing of dynamic biochemical reactions, cell sensors become more useful for many studies, such as measurements of protein folding or neural activity.

As described in the Journal of the American Chemical Society,* a NIST biophysicist working at JILA and a collaborator at the University of Colorado Boulder (CU) developed a microfluidic system that records biochemical reactions over a time span of milliseconds to seconds in living human cells modified to act as FRET (fluorescence resonance energy transfer) sensors.

The fast, flexible system uses lasers to measure sensor signals at two points in time at a rate of up to 15 cells per second. Statistical data, such as the average value of the FRET response for thousands of cells, can be collected in minutes.

"Our system is the first one that measures FRET response times at the single-cell level, while at the same time measuring over many cells," says JILA Fellow Ralph Jimenez, whose research group built the optics, microfluidics, electronics and other hardware.

JILA is a joint institute of NIST and CU. Jimenez is collaborating with Amy Palmer, an assistant professor in CU's Department of Chemistry and Biochemistry, who handled the molecular design and cell-biology aspects of the project.

The FRET technique relies on reactions that occur between large biological molecules in close proximity to each other. One molecule absorbs light energy from a laser and transfers this energy to the nearby acceptor molecule. The acceptor molecule then releases this energy as light (fluorescence) at a characteristic wavelength that is different from the original laser light. Measurements of this fluorescence indicate the extent of the energy transfer. FRET can be used to study many types of cellular processes. In these experiments, the researchers were interested in the type and concentration of metal ions within cells, which can affect important cell processes. The JILA/CU experiments used cells genetically modified to take up particular metal ions and signal changes in their concentrations by altering the FRET signals.

The researchers made a microfluidic device with a flow-control valve system that mixes cells and metal-containing chemicals in just a few milliseconds. The cells then pass single file through two blue laser beams that excite the FRET fluorescence signal at different locations in the device. With precise flow control and flexible device design, cell travel time between the two locations can be varied from 1 millisecond to 10 seconds. Scientists measure the FRET signal changes within individual cells between the two locations.

"FRET is an important measurement technique used in bio-imaging, so it's great that NIST could begin to contribute to measurements of the fidelity of FRET-based sensors," Jimenez says. "We have a lot more work planned for the future with this instrument."

The project is part of the research team's effort to develop cell sensors with improved optical, physical and chemical properties and to enable detection of very faint signals in living cells. The work was supported in part by a CU-NIST seed grant, the National Institutes of Health and the National Science Foundation.

* H. Ma, E.A. Gibson, P.J. Dittmer, R. Jimenez and A.E. Palmer. High-throughput examination of FRET-detected metal-ion response in mammalian cells. Journal of the American Chemical Society (JACS). Published online Jan. 19, 2012. (Communication) DOI: 10.1021/ja2101592.

SOURCE: National Institute of Standards and Technology

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Good Timing: NIST/CU Collaboration Adds Timing Capability To Living Cell Sensors

Forest Park's Braunecker headed to Harvard

Ben Braunecker leapt at the chance to play football and study biochemistry at Harvard University.

"I think Harvard is at the top," said Braunecker, a Forest Park High School senior who signed papers committing to the Crimson on Thursday. Ivy League schools do not give athletic scholarships, but Braunecker is receiving academic aid.

"They won the Ivy League championship and have great athletics. They are also one of the most prestigious universities overall in the U.S. and the world."

Ben Braunecker

Braunecker turned down a full athletic scholarship from Southern Illinois University.

"Obviously going to school for free and playing football did spark my interest," said Braunecker, who was also recruited by Columbia, among others. "But I rely on the '4 and 40 rule.' You're only playing football for four years and ultimately you have to decide what you're going to do for the next 40."

Braunecker, a 6-foot-4, 215-pounder who is a straight-A student and class valedictorian, caught 27 passes for 644 yards, a 23.9 average, including seven touchdowns, in earning the Courier & Press All-Southwestern

Indiana Player of the Year honors. He was the Pocket Athletic Conference Most Valuable Player and named honorable mention all-state.

Braunecker averaged 34 yards per kick return, including two touchdowns, and 36.5 yards on four punt returns. Braunecker also had three interceptions playing defensive back.

Harvard is looking at him as a "hybrid," a combination of split end and tight end.

Braunecker, who also plays basketball and is a member of Forest Park's track and field team, will improve as he specializes in one sport, said Rangers football coach Terry Wagner.

"He'll have time to reach his full potential," Wagner said. "For us, he never came off the field. They want him to put on 15 more pounds and develop into an even better player."

Wagner said Braunecker was looking for a challenge.

"Academics is very important in his life," Wagner said. "He realizes that school comes first and it's a school that is rich in tradition and he got caught up in all that."

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Forest Park's Braunecker headed to Harvard

News digest: MathAcrossCampus Friday, Honor: Charles Peck and Chrysan Gallucci, English language courses

Feb. 9, 2012

Biochemistry prof showcases applications of math Friday in MathAcrossCampus
Tomorrow the MathAcrossCampus lecture series presents David Baker, a UW biochemistry professor, in an interdisciplinary public talk titled “Computing Proteins.” Baker will describe research looking at why proteins, which could take on a vast number of possible configurations, fold to single unique structures that allow them to carry out their functions. He will describe his efforts to predict these structures in the lab, through the distributed computing project Rosetta@Home, and with the online game Foldit, as well as research on designing new proteins to address 21st-century challenges.

The lecture will be Friday, Feb. 10, from 2:30 p.m. to 3:30 p.m. in Kane Hall 210. MathAcrossCampus showcases applications of mathematics, with a special emphasis on the growing role of discrete methods in math applications.

Charles Peck’s teacher-education article honored
Change is hard, in teacher education programs as in all things. If new regulations and state mandates are viewed as undercutting a program’s local control, this can weaken the very staff motivation needed to implement changes.

This dampening effect may be lessened if the focus of reforms is shifted from top-down compliance to collective inquiry, local knowledge is valued and changes are seen as opportunities to clarify and improve the program.

That’s according to finding of a December 2010 research paper by Charles Peck, a UW professor of education, and colleagues that has been named outstanding “Journal of Teacher Education” article by the American Association of Colleges for Teacher Education. Peck’s co-authors are Chrysan Gallucci, UW professor of education, and Tine Sloan of the University of California, Santa Barbara.

The researchers studied a teacher education program in the University of California system for 18 months as program leaders considered implementation of new legislation creating a two-tier credential system and new state standards for teacher preparation.

Reviewers said Peck and co-authors “constructed a rich, descriptive account of the events and the impacts of the policy implementations as they unfolded in a local context,” adding that “the authors’ stance of inquiry, rather than compliance, provided the field with a portrait of how systematic, programmatic research can greatly benefit the educator preparation profession.”

The award will be presented at the association’s annual conference, Feb. 17-19, in Chicago.

Online, on-site English language courses for UW employees
The UW International & English Language Programs offers quarterly online and on-site courses for those who are primarily non-native speakers of English.

Online courses are available for those who want to improve their grammar and vocabulary in academic, business or technical writing.  All of the courses have weekly interactive exercises and short assignments. Instructors respond to assignments within two business days.

Evening on-site courses focus on improving conversational skills and preparation for the English tests through organizations such as Test of English as a Foreign Language or International English Language Testing System. There are also daytime courses in reading, writing, grammar, speaking, listening, and vocabulary and idioms.

UW International & English Language Programs can customize courses for non-native speakers in the workplace. For example, courses can be designed for such areas as pronunciation and fluency, assisting clients by telephone, presentation skills and the language of meetings, e-mail communication and job-specific communications.

For more information, call 543-6242 or e-mail uwelp@u.washington.edu.

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News digest: MathAcrossCampus Friday, Honor: Charles Peck and Chrysan Gallucci, English language courses

No entry without protein recycling: RUB researchers discover new coherence in enzyme transport

Public release date: 10-Feb-2012
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Contact: Dr. Ralf Erdmann
Ralf.Erdmann@rub.de
49-234-322-4943
Ruhr-University Bochum

The group of Prof. Dr. Ralf Erdmann at the Ruhr-Universit?t Bochum (Faculty of Medicine, Department of Systems Biochemistry) discovered a connection of peroxisomal protein import and receptor export. In the Journal of Biological Chemistry, they disclosed that enzymes only get imported into certain cell organelles (peroxisomes) upon coupling of their import to the recycling of their transport protein (receptor).

Multi-functional tool peroxisome

Peroxisomes do not have their own DNA. Thus, all peroxisomal proteins are coded within the nucleus and imported into the peroxisome after their synthesis is completed. The Erdmann lab investigates this process in detail. Peroxisomes contain more than 50 various enzymes in total which e.g. decompose fatty acids and dispose hydrogen peroxide or plasmalogens, the main phospholipid of the white matter of the brain. A disruption of their function does not only cause severe metabolic disorders, it can even lead to death of newborns.

Export signal controls recycling

Dynamic receptors recognize and escort the enzymes destined for the peroxisome to the organelle where they attach to the membrane. Then the receptor-enzyme complex disassembles and the enzyme is transported across the peroxisomal membrane. Afterwards, the receptor is transported from the membrane back to the cytosol. This recycling is controlled by the attachment of the small protein ubiquitin to the receptor, which functions as an export signal.

Modification as a safety barrier

The team of Prof. Dr. Ralf Erdmann studied a certain peroxisomal receptor, which consists of a targeting unit (Pex18p) and an enzyme-binding unit (Pex7p). The scientists discovered that ubiquitin modifies Pex18p in order to enable the receptor to return to the intracellular liquid. Only when the targeting unit of the receptor is exported from the membrane, the import of the cargo-loaded enzyme-binding unit takes place. This result supports the export-driven-import model, previously proposed by the Erdmann group.

###

Bibliographic record

A. Hensel, S. Beck, F. El Magraoui, H.W. Platta, W. Girzalsky, R. Erdmann (2011): Cysteine-dependent ubiquitination of Pex18p is linked to cargo translocation across the peroxisomal membrane, Journal of Biological Chemistry, doi: 10.1074/jbc.M111.286104

W. Schliebs, W. Girzalsky, R. Erdmann (2010): Peroxisomal protein import and ERAD: variations on a common theme, Nature Reviews Molecular Cell Biology, doi: 10.1038/nrm3008

Further information

Prof. Dr. Ralf Erdmann, Department of Biochemistry Systems, Faculty of Medicine of the Ruhr-Universit?t Bochum, 44780 Bochum, Germany, Phone: +49/234/32-24943 Ralf.Erdmann@rub.de

Click for more

Department of Biochemistry Systems
http://www.ruhr-uni-bochum.de/physiolchem/system/index.html.en

Previous press information on the topic
http://aktuell.ruhr-uni-bochum.de/pm2011/pm00233.html.en

Figure online

A figure related to this press release can be found at http://aktuell.ruhr-uni-bochum.de/pm2012/pm00024.html.en

Editor

Marie-Astrid Reinartz

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No entry without protein recycling: RUB researchers discover new coherence in enzyme transport

#30 Biochemistry Lipids and Membranes Lecture for BB 451/551 Winter 2012 – Video

13-01-2012 17:19 A lecture by Kevin Ahern of Oregon State University to his BB 451/551 class. See the full course at oregonstate.edu This course can be taken for credit (wherever you live) via OSU's ecampus. For details, see ecampus.oregonstate.edu Download Metabolic Melodies at http://www.davincipress.com Related courses include BB 350 - oregonstate.edu BB 450 - oregonstate.edu BB 100 - oregonstate.edu Topics covered include lipids,lipid bilayer, membrane, plasma membrane, cell, barrier, glycerophospholipids, phosphoglycerides, phosphatides, phosphatidyl compounds, serine, ethanolamine, inositol, sphingolipids, sphingomyelin, nerve membrane, brain, cholesterol, membrane fluidity, cerebrosides, gangliosides, micelles, integral membrane protein, peripheral membrane protein, associated membrane protein, anchored membrane protein, structure prediction, bacteriorhodopsin.

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#30 Biochemistry Lipids and Membranes Lecture for BB 451/551 Winter 2012 - Video

#29 Biochemistry Citric Acid Cycle II Lecture for BB 451/551 Winter 2012 – Video

12-01-2012 08:16 A lecture by Kevin Ahern of Oregon State University to his BB 451/551 class. See the full course at oregonstate.edu This course can be taken for credit (wherever you live) via OSU's ecampus. For details, see ecampus.oregonstate.edu Download Metabolic Melodies at http://www.davincipress.com Related courses include BB 350 - oregonstate.edu BB 450 - oregonstate.edu BB 100 - oregonstate.edu Topics covered include citric acid cycle, oxidation, respiration, reduction, malate, oxaloacetate, NADH, NAD+, FAD, FADH2, respiratory control, regulation, pyruvate dehydrogenase, phosphorylation, kinase, phosphatase, glyoxylate cycle, malate synthase, isocitrate lyase, plants, yeast, fungi, bacteria

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#29 Biochemistry Citric Acid Cycle II Lecture for BB 451/551 Winter 2012 - Video