Does when you eat matter?

Everyone has an internal clock, called the circadian rhythm, that controls wake/sleep cycles, body temperatures, brain activity, and changes in hormone levels throughout the day.  Disruption in these circadian rhythms can alter metabolism.  In the latest issue of Cell Metabolism (epub ahead of print June  2012 DOI 10.1016/j.cmet.2012.04.019), Dr. Megumi Hatori and colleagues investigated how feeding patterns, in particular time restrictions to eating, can alter metabolism and the expression of genes that control the circadian rhythm.  

Mice were divided into four groups as follows:

1. Normal calorie diet, freely accessible all day
2. Normal calorie diet, limited access
3. High fat diet, freely accessible all day
4. High fat diet, limited access

Mice are nocturnal and were placed on a 12 hour light/dark cycle.  For groups 2 and 4, food was available from 1 hour after lights off (waking) until 3 hours before lights on (sleeping).  

Their data were intriguing.  Mice in both high fat diet groups consumed equivalent numbers of calories over a 24 hour period.  Those with free access appeared to eat all day with no spike in intake at any regular time period, while those with limited access consumed their calories only during the 8 hour period.  

As expected, mice with unlimited access to the high fat diet gained significant weight compared with either of the normal calorie diet groups.  Conversely, the mice on the high fat diet with limited access did not have the same weight gain as the unlimited access group.  Indeed, mice in the time restricted groups were lower weight than those with unlimited access.  When comparing the high fat diet groups, the mice with limited food access did not become obese as did the unlimited access mice. In fact, their weight was only slightly higher than the normal calorie diet groups.  In addition, the time restricted high fat diet group also retained sensitivity to insulin and did not exhibit liver problems as seen in the unlimited high fat diet group.

This very interesting study suggests that circadian rhythms control metabolism and restricting food intake to regimented periods during the day can help to keep the metabolism strong and avoid excessive weight gain.  This is a small study in mice, but could have implications in human dieting and the control of weight gain.

Science for the public

by Jasper Manning, Ph.D.

Each day large amounts of scientific information is disseminated from mass media to the general public. This includes healthy-related studies and novel scientific breakthroughs with the aim of educating, informing and improving the quality of life. Much of this information comes from pundits and medical reporters who support their ideas with well researched facts. However, in some instances, facts are misconstrued in order to support a specific agenda(s) of a political lobby or industry i.e. global warming or endangered species lists. In addition, the summary of published information by medical writers sometimes is erroneous due to lack of available print space and/or time set aside for an article or misinterpreted perhaps due to a lack of knowledge about a topic. In the end, an article that is unable to convey to laypersons the benefits or detriments of a study defeats the intended purpose of the article. Howy Jacobs, a distinguished professor of molecular biology at the Institute of Medical Technology (IMT), University of Tampere and senior editor at EMBO Reports recently suggested that a miseducation of the masses through mass media is due to the misconnection between science and the media (Jacobs, 2012) and believes that the responsibility of educating medical writers falls on scientists. Once this can occur, the reader, has a better chance of receiving complete and concise information. 

Jacobs illustrates the lack of clearly presented information to the general population by relating a recent conversation that he had with a southern Alaskan Bed and Breakfast owner. The owner espoused that climate change was not a reality and had no affect on wildlife specifically in the case of the polar bear. Jacobs notes that after some fact-checking, he found published data of comparative mitochondrial DNA sequence of polar bears and brown bears that supported that environmental stress (Edwards, et al, 2011) may have influenced a recent introgression between the two species. Dr. Jacobs chose not to challenge the beliefs of the owner (perhaps many scientist choose to sit out these arguments), but realized that the scientific data is available although public awareness is lacking. This is a plus for lobbying groups and others since a uninformed public can be easily influenced by those who have a vested interest in exploiting the environment. He astutely points out that science should not support political argument/agenda, nor “prove” a hypothesis but accumulate, interpret data and form a predictive model based on the interpretation. In his opinion, the media should explain this process used by scientists and report the findings legibly or risk painting a picture of science as a confusing and perhaps dishonest profession as in the case of global warming.

 All in all, the take home message of the Jacob's editorial is that scientists must be able to better convey scientific results to the media in a clear and comprehensible way. On the other side of the coin, the media has a responsibility to become more knowledgeable in basic science and the aspects of the scientific method. He believes that miscommunication is the primary problem and scientist must learn to better explain interpreted data to the world and correct poorly presented interpretations that are published in the media.

 It is refreshing that scientists such as Howy Jacobs understands that scientist are the key to explaining the latest breakthroughs and correcting errors in summarized studies that are published in the public domain. Blogs such as N3science communications is a good starting point as well. Take a read and pass it along. Scientists are trying to educate, now it is your turn to read and understand what is happening with science around you.

 REFERENCES Howy Jacobs EMBO reports (2012) 13, 471;doi:10.1038/embor.2012.56 Edwards CJ et al 2011) Curr Biol 21:1251-1258

KRAS mutation responds to anti-folate therapy

While there is still a way to go in designing personalized medicines, increasingly some interesting (and surprising) findings are unfolding. Indeed, it is becoming increasingly evident that gene mutations, changes in protein expression, or changes in the location of proteins in the cell can alter how the response to treatment. A recent study, presented at the American Association for Cancer Research Annual meeting, demonstrated that a mutation in KRAS, a gene commonly mutated in some cancer patients, reduces the responses to chemotherapy. This is, in and of itself, not welcomed news -- however, this study found that such KRAS mutations improve the response to anti-folate drugs (drugs not commonly used to treat lung cancer). Therefore, depending on the mutation present and the number of copies of that mutant protein that exist in the cell, anti-folate treatment may help stop cancer growth. The bigger picture that emerges from this study is that a mutation that is detrimental when common chemotherapies are employed, in fact, be quite beneficial when other therapies are considered.

http://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=2739

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Is the increased spending on cancer care in the US "worth it"?

This was the question asked by health economy scientists at the University of Chicago, the University of Southern California, Precision Health Economics, and Bristol-Myers Squibb in a recent publication in Health Affairs (April 2012, 31:667-675). Spending on cancer care in the US is almost double the amount that is spent in Europe ($70,000 vs $44,000 per cancer patient). Many have debated if this increased spending is evidence of waste and unnecessary excess of the US health care system or if it equates to improved survival for patients. In this paper, Tomas Philipson and colleagues evaluated the financial cost and gain from increased spending on cancer care. Interestingly, they found that the increased spending in the US averted cancer-related deaths as seen in decreased mortality and led to improved survival rates. According to their calculations, the authors estimate that an increase of $20,000 in cancer spending per patient results in a 1 year increase in survival. This may be due to improvements in technology, more targeted therapy that is incorporated into therapeutic care faster, and/or increased screening procedures. While they cannot dismiss other factors that are not related to care delivery, such as improved diet and increased exercise, the evidence presented suggests that a correlation between spending on cancer care and survival does exist. It cannot be argued that excesses and inefficiencies in the US health care system do still exist, however this analysis suggests that improvements in detection, prevention and treatment - while costly - produce favorable outcomes.

http://content.healthaffairs.org/content/31/4/667.abstract

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High calorie diet and memory

I just heard about the latest research connecting memory loss with a high calorie diet and thought I’d check it out. An abstract of the scientific work was presented at the American Academy of Neurology annual meeting on February 12, 2012. The team, led by Dr. Yonas Geda, evaluated the dietary intake and cognitive status of over 1200 70 - 89 year old patients over 1 year. No participants had dementia at the onset of the study. Based on their total caloric intake per day, patients were divided into one of three groups - low, middle, or high calorie diets. Those in the high calorie intake group (>2143 to 6000 calories per day) had doubled their chances of developing Mild Cognitive Impairment (MCI), a pre-dementia condition. To see the abstract, visit http://www.aan.com/globals/axon/assets/9279.pdf. It will be interesting to read the full paper when it is published.

Could donating 1% improve the health of 100%?

Several interesting articles have surfaced lately. First among these is an article by Dr. Sally Rockey, Deputy Director for Extramural Research at the National Institutes of Health. In it, she annotates the decline in success rates for researchers of obtaining NIH grant funding and explains some of the underlying reasons for this decline. Indeed, in the last 10 years or so, the number of applications to the NIH for grant funding has increased dramatically. In 1998 NIH received 24,151 applications, but by 2011, this number soared to 49,492. The budget for the NIH did increase over this same period (from just over $13 billion in 1998 to $30 billion in 2011), however this increase has not allowed for a sustained increase in the success rates of obtaining funds. This success rate has dropped from a high of 32% to a new low of 18%. This number represents all funds, but funding rates for new grants are much lower (very far south of 10%).

The second article, or rather a series of articles, was published in Nature Magazine this week. In this series, the idea of science philanthropy and scientists fundraising for themselves from wealthy donors or from a large number of smaller donors was discussed. It is an interesting idea. Scientists are beginning to use websites like Kickstarter where they pitch their lab research ideas and those interested make donations to fund these projects. Sure, this isn’t the traditional peer-reviewed technique used by NIH and other funding agencies, however it does connect scientists to the public. Besides, peer-review isn’t the only model.

Funding science is worth the investment. In 2010, NIH granted almost 9,500 new grant awards and distributed $22 Billion to investigators for both new and continuing grants. It is estimated that this allocation yielded $69.2 Billion in economic activity in the US and created 484,939 jobs. This equates to a rate of return estimated at 32- 43%. Federal investment in research is highly productive. Not only does public funding of research produce a great rate of return on the investment, but publicly funded research also stimulates a additional 25 - 32% increase in privately funded medical research.

I think there could be a new way to fund science research that can work in parallel to the NIH and other public funds. The US has a strong history of philanthropy among private citizens and companies. What if individuals and companies -- from actors to Wall Street firms -- were to contribute to a centralized non-profit that funds basic and translational research. This could be styled like NIH in that it can fund a broad range of research areas, but can employ and explore new ways to evaluate the science and distribute the funds. What if companies and individuals set aside just 1% of their yearly profits or charitable contributions to establish such an organization? This money can be used to fund young emerging scientists and new ideas that may help improve the lives and health of everyone. Isn’t 1% a small price to donate? This might not be what has always been done, but isn’t it time to start looking for new ways to help fund science?

Have a comment? Email me at jck@n3scicom.com or post it here.


References:

http://news.sciencemag.org/scienceinsider/2012/01/nih-examines-what-drove-its-grant.html#more

http://www.nature.com/news/finding-philanthropy-like-it-pay-for-it-1.9815

http://www.nature.com/news/alternative-funding-sponsor-my-science-1.9814

http://www.nature.com/nature/journal/v481/n7381/full/481260a.html

NIH - history of budget allocations
http://officeofbudget.od.nih.gov/approp_hist.html

“Benefits of medical research and the role of the NIH”, May 2000, Office of Senator Connie Mack.

“An economic engine: NIH research, employment, and the future of the medical innovation sector.” Dr. Everett Ehrlich, United for Medical Research.

n3 science communications

A step closer to a new treatment for Huntington's Disease

Researchers at the University of California, Davis have just published a really interesting paper in Molecular and Cellular Neuroscience. Huntington’s Disease is a neurodegenerative disease that arises when an expansion of trinucleotide repeat (CAG) in the gene that encodes the huntington protein (called HTT) occurs. The CAG repeat is found naturally in the HTT gene, however in patients with Huntington’s Disease, this repeat can be found in stretches containing greater than 30 (and up to hundreds) repeats.

Currently, there is no cure for Huntington’s. Ideally, being able to decrease or eliminate the expression of the mutant HTT gene in the specific neurons of Huntington’s patients would work to reverse or cure the disease. Unfortunately, this type of therapy isn’t possible yet. In 2006, a new technique to switch off gene expression (and protein production) was developed by Drs. Mello and Fire (they shared the Nobel Prize for this!) called RNA interference, or RNAi. In a nutshell, this technique blocks the translation of RNA molecules into protein and results in decreased protein amounts overall. There are several limitations to using this RNAi technique in humans as a disease therapy. Among these are -- preventing the degradation of RNAi probes, developing ways to target the RNAi to the specific cell, and getting the probe into the appropriate cell. In this latest paper, Dr. Nolta and colleagues have taken a step closer to solving one of these obstacles; getting the RNAi probes into the neurons and decreasing HTT expression. They placed the RNAi probes into mesenchymal stem cells and used these cells as carriers to transport the probes to the neurons with the HTT expansion. Mesenchymal stem cells (MSGs) are excellent carriers because they can be harvested from bone marrow or fat tissue of patients (therefore MSGs are safe and have anti-inflammatory effects) and can be expanded in cell culture. Additionally, MSGs have been shown to transfer fairly large organelles and molecules from one cell to another. In this paper, MSGs were infected with the RNAi probe and used to deliver that probe to the HTT expressing neuron in the same culture. Once the probe was successfully transferred to the neuron, levels of HTT gene expression declined, eliminating one of the factors that leads to the development of Huntington’s. There is still more work to be done before this is an actual therapy for those with Huntington’s, however this paper helps move the idea one step closer to reality.

http://www.ncbi.nlm.nih.gov/pubmed/22198539

questions or comments? Feel free to email me directly -- jck@n3scicom.com


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RNA binding proteins: a new target for therapy?

In the ongoing effort to develop new therapy for diseases including cancer, identifying new drug targets in diseased cells remains the focus of much scientific research. In recent years, new potential drug targets and new molecules have been identified. These include proteins that are over-expressed or not expressed in disease cells compared with normal or gene variations that alter the shape or function of a protein in a cell. Examples of such are plentiful -- from overexpression of the protein Her2 in breast cancer, to the lack of expression of the tumor suppressor gene p53 in numerous cancer types.

In the last 10 years, new molecules called micro-RNA (which are small stretches of RNA molecules that can prevent proteins from being expressed) have stolen the spotlight and hold the potential to be developed into a new class of drugs that specifically target their function. This field is exploding and providing new insight into how genes and proteins are expressed. It now appears that the control of protein levels in a cell involves even more players.

Now, it seems that a newly scrutinized class of proteins, called RNA binding proteins, are emerging as a new target that can be exploited to develop new therapies. These RNA binding proteins are involved in RNA binding (couldn’t guess that from the name!). They are able to carry RNA to different locations in the cell, to increase or decrease the expression of RNA or protein, and, it now seems, have altered expression, function, or location in diseased cells including inflammation and cancer. RNA binding proteins can interact with miRNA to control the level of the bound RNA or the level of protein expression. Understanding their role in gene expression does add yet another layer to the complexity of the cell, but may lead to critical insight into how to control expression of important proteins.

Recent review articles and commentaries have shown the growing number of diseases that have altered RNA binding protein activity. Maybe they are an emerging new avenue for therapy? Check out these reviews:

http://onlinelibrary.wiley.com/doi/10.1002/wrna.62/abstract;jsessionid=1E2822BB213813E5BA84E8888B9F8AB9.d01t01


http://www.springerlink.com/content/35862187j2587526/


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How accessible are open-access journal articles?

The world of science publishing is changing, dramatically. The internet has now produced a plethora on online-only journals that have been instrumental in aiding the distribution of the latest scientific results. So too has the relatively new idea of open-access journals. Traditionally, experiments and data were published in peer-reviewed subscription based journals. Most schools and libraries owned subscription plans to hundreds of titles and provided access to the employees so they could easily (and affordably) conduct their research and hence, do their jobs. In the late 2000s, things began to change. Funding agencies who provided the research dollars to conduct this research were getting increasingly frustrated that they had paid for this work to be done, but were unable to read the results of these efforts without shelling out a tidy sum to gain access to the journal. This opened the door for open-access journals and publishing. In 2008, the National Institutes of Health invoked a new policy: that the work paid for by NIH funds had to be “deposited” in a centralized database, PubMed Central, so that it was publicly available. Open-access journals that allow anyone with access to the internet to download a complete scientific article for fee, were born. Unlike traditional journals that charge a subscription fee, open access journals charge a review fee for each paper that is submitted for review. This way they can pay for the publication of the work without charging a subscription fee.

Although open-access journals provide access for everyone to the scientific research publishing on their pages, to some these research papers are far from accessible. Science is written in a very technical language, so while these journals provide access to the very scientific papers, few of these articles are translated into a more accessible language. This is not the fault of the scientists or the journals, but it does point to a need to convert this scientific information so a broader audience can appreciate the work that is being done. Open-access is a good idea, but maybe there should also be an open-access journal that helps review the science and translates it so it is more accessible to a much broader audience.

CDC provides millions for HIV/AIDS prevention

The Centers for Disease Control and Prevention (CDC) announced today that it will be awarding $339 million to state Health Departments for HIV prevention services (along with new treatment guidelines). This is all part of a new five year effort on behalf of the CDC to provide funds to prevent the spread of HIV/AIDS. In light of the data from the HIV treatment as prevention clinical trial (HTPN 052) published last year, this new approach seems like a good approach to reducing the spread of HIV/AIDS in the US.

HTPN052 was the clinical trial run by Dr. Myron Cohen at the University of North Carolina at Chapel Hill. In this trial, researchers examined if HIV/AIDS treatment, called anti-retroviral therapy, given when patients were in the early stages -- while they were infected with HIV but had yet to develop AIDS -- could reduce the transmission of disease to uninfected partners better than if treatment were delayed until AIDS had fully developed. In other words, could current HIV/AIDS treatments be given earlier as a preventative agent to stop the spread of the virus to uninfected partners. Results from this clinical trial were stunning. (So stunning that these results earned this clinical trial the distinction of being named the Breakthrough of the Year! by Science Magazine). Researchers detected a 40% decrease in infection rate when the drug was given as a preventative manner. Although some issues regarding distribution and cost of these drugs still exist, these results could mark the turning point in HIV/AIDS infection rates.

For more information, visit:

the CDC
http://www.cdc.gov/nchhstp/newsroom/HDFundingPressRelease.html

or information about the Breakthroughs of the Year by Science Magazine
http://www.aaas.org/news/releases/2011/1222sp_boy.shtml


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Losing ground: what will happen to young scientists in academics?

The economic turndown and subsequent reduction in federal funding of basic science research is wreaking havoc on the young scientists in academic institutions. Many young faculty who started their academic faculty jobs in 2006 - 2007, just before the meltdown, are now finding themselves looking for new careers. Because of the reduction in federal funding and the increased competition for the ever-limited grants that still exist, these highly trained professionals who are just starting their careers are now looking for new opportunities outside of academics and research. They are being forced to leave faculty positions to find work doing anything they can. It is no longer feasible to meet the requirements of the contracts they signed 5 years ago and universities cannot or will not support them during these hard times. The outcome of this decline will be that universities will be left with an aging faculty (who will not or cannot retire) and little new blood to provide new ideas and perspectives. Even worse, as the aging faculty retire (eventually), there will be no one there to take over. Few junior faculty will be employed at universities that understand the workings of academia to be able to lead these institutions when they are needed to do so.

Many articles about this have been appearing in the scientific press, but now more are being published in major newspapers. Dr. Carol Greider, a Nobel Laureate and professor at Johns Hopkins recently addressed this very issue in an article in the Baltimore Sun. (http://articles.baltimoresun.com/2011-12-22/news/bs-ed-scientists-20111222_1_young-scientists-medical-research-funds-research) Although she did not address how to help rectify this situation, I think it is time to start thinking about alternative ways to fund basic research.

An increasing number of people feel that funding science is not a priority. I beg to differ. Science is an economic engine that has propelled the US for the past century. The rate of return on the federal investment has been in the range of 30 - 40%. Not too shabby -- throw in the advancement in technology (better scanning equipment, imaging machines, and treatment options to name a few) and the contribution of federally funded science is undeniable. I reiterate, maybe it is time for new avenues to fund science research should be explored.


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