House Approves Austere Budget Resolution

BLUEPRINT 2014 COVER.pagesThe fact that an overall budget blueprint for 2015 was agreed upon by the House and Senate in December as part of the 2014 budget process has not stopped the House from approving an alternative FY 2015 budget resolution by a vote of 219-205. Written by Chairman Paul Ryan (R-WI), the budget blueprint, referred to as the Path to Prosperity, adheres to the $1.041 trillion discretionary spending limit for FY 2015 and the split between the defense and non-defense spending caps negotiated last December. However, it includes severe cuts to non-defense discretionary programs in order to increase defense spending for FY 2016 and beyond.

During a hearing in the House Budget committee, Budget Committee Ranking Member Chris Van Hollen (D-MD) stated that the budget resolution “makes historically reckless cuts in areas that help power our economy – education, scientific research, innovation, advanced manufacturing, and diverse energy sources.”

The Senate, led by Democrats, does not plan to consider the House’s Budget Resolution but the vote demonstrates the House’s ongoing commitment to continue to cut spending on discretionary programs, which includes spending on research.

Both the House and Senate are out of session. Members will return to Washington the week of April 28th and will resume consideration of FY 2015 Appropriation bills at that time.

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Puzzling Permeating Peptides

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Antimicrobial peptides are toxins that either (a) disrupt the integrity of cellular membranes or (b) instigate their own passage through these membranes on their way to intracellular targets. However, the mechanisms by which these peptides interact with a lipid bilayer (the defining component of a cell membrane) are poorly understood. Furthermore, given that a characteristic of lipid bilayers is to prevent the permeation of charged solutes, it remains puzzling why antimicrobial peptides are largely ionic.

In our letter, we use massively repeated computer simulations to quantify the favorable insertion of the antimicrobial peptide indolicidin into a lipid bilayer. The simulations suggest that a single molecule of indolicidin is capable of thinning and permeabilizing the lipid bilayer. The balance of hydrophobicity, charge, and structural disorder in this antimicrobial peptide appears to be well-suited to disrupt cell membranes, even in the absence of peptide aggregation or the formation of an ordered structure. Moreover, we emphasize the necessity of lengthy and massively repeated simulations to attain and gauge convergence of the calculations.

The image shows a simulation snapshot in which monomeric, intrinsically disordered indolicidin (yellow) resides in the bilayer’s hydrophobic core (white) and interacts with zwitterionic headgroups (brown) in both leaflets, drawing them inward and deforming the bilayer, causing the influx of water (cyan). Water and lipid in the foreground have been omitted for clarity.

We see science-as-art in cases where an image conveys a profound new scientific insight. That is, the beauty of the image does not solely arise from color, composition, or artistic flair, but also, crucially, in the novel understanding that it provides or represents. It is only in this respect that we consider ourselves artists. As such, our aspirations for our next science-as-art submission are intimately related to our basic scientific goals.

Please visit www.pomeslab.com for more information on our research interests.

–Chris Neale

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Red Blood Cell Adhesion in Sickle Cell Disease

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Millions worldwide live with sickle cell disease, the most common inherited blood disorder. Sickle cell disease is due to a single-point mutation in the ÿ-globin gene resulting in the production of abnormal hemoglobin. In the deoxygenated state, hemoglobin polymerizes to form relatively stiff filaments forcing red blood cells to assume an irregular shape. It is these “sickled” red blood cells that are thought to significantly contribute to, if not initiate, occlusion of small blood vessels resulting in microvascular infarction, severe pain, widespread organ dysfunction, and early mortality.  The hallmark of the disease is the development of spontaneous, intermittent, disabling episodes of severe pain called vaso-occlusive episodes.

Our article discusses adhesion of normal and sickle cell disease human erythrocytes to endothelial laminin.  Erythrocyte adhesion to endothelium is thought to be a critical mediator of the complicated process of vaso-occlusion in sickle cell disease. This translational work is a collaboration between investigators at the schools of Engineering and Medicine at the University of Connecticut.  When our article was accepted for publication, we thought that an image on the journal cover would be a good way to attract attention to this devastating disease and to show, at least partially, the complexity of one of its major consequences in the circulatory system. The image was created by Kostyantyn Partola, who is a first-year Ph.D. candidate in our lab. It is a three-dimensional depiction of normally and abnormally shaped sickled red blood cells interacting with endothelial cells as well as white blood cells and platelets in a human blood vessel cross-section. Some of the sickled cells are adherent to the endothelium and partially obstruct blood flow, while other cells are shown flowing freely within the blood vessel. We tried to create an interesting picture by illustrating how the interaction of cells can mediate vasoocclusion.

Please visit the website of the Cellular Mechanics Laboratory at the University of Connecticut and the Comprehensive Sickle Cell Clinical and Research Center at the University of Connecticut Health Center for more information on our research.

–Jamie Maciaszek, Biree Andemariam, Krithika Abiraman, and George Lykotrafitis

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Brain Injury Awareness Month: Understanding the Underlying Neurobiological Mechanisms

Brain Injury Awareness Month:  Understanding the Underlying Neurobiological Mechanisms

Each month, we highlight ongoing biophysical research related to a disease/condition for which advocates are trying to raise awareness.  Often, in the push to find the next cure/treatment for a given condition, the public forgets that those cures and treatments are based on fundamental research conducted to understand how systems, both large and small, within our bodies work.  That is the work that Biophysical Society members are conducting everyday in their labs.

Since March is Brain Injury Awareness Month, we asked BPS member Les Satin, University of Michigan, to share his research on brain injuries with us. More information about brain injuries and the activities associated with the awareness month is available from the Brain Injury Association of America.  Given that 1.7 million Americans sustain a brain injury every year, it is clear that fundamental research in this area is needed to improve treatments and outcomes for those individuals.

What is the connection between your research and brain injuries?

Mild to moderate traumatic brain injuries are a major health problem but there are currently no effective therapies for them. As these injuries involve changes in neuronal function and synaptic communication between surviving neurons, better understanding the underlying mechanisms may result in new pharmacologic treatments to reverse the alterations caused by TBI and restore normal function. In our research, we directly injure cortical pyramidal neurons and glia in vitro by mechanically deforming the cells to mimic the forces encountered in brain following a traumatic brain inury (TBI), and then we assess their functional changes.

Why is your research important to those concerned about brain injuries?

As there are currently no effective pharmacological approaches to treat patients with TBI, our work may reveal new strategies to treat patients with TBI to alleviate deficits in cognition, memory, mood and motor function.

How did you get into this area of research?

I was originally trained in neurobiology and always was interested in neuronal function and synaptic transmission but my involvement in TBI research came about after meeting researchers and clinicians at my former institution, Virginia Commonwealth University, which has been a center for TBI research for decades. Many of my colleagues there urged me to get involved because we knew so little about how TBI alters neuronal electrophysiology, an area in which I have expertise. This seemed like a good area of study because we could make novel contributions to a very important, and poorly understood clinical problem. I remain convinced that the field continues to suffer from the dearth of basic research performed into the underlying neurobiological mechanisms.

How long have you been working on it?

My lab first started working on TBI in the mid 1990s when my first graduate student Steve Tavalin found that stretch injured neurons exhibited a delayed depolarization that resulted from an NMDA receptor dependent loss of electrogenic Na pump activity. From that time forward, our continual work has led to a string of publications mainly involving changes in both excitatory and inhibitory synaptic function.

Have you had any surprise findings thus far? 

Yes! Almost all of our findings have been surprises! Mildly injured neurons show a variety of changes after injury, yet these all seem to be very specific: we found reduced fast           desensitization of AMPA receptors, reduced Mg2+ block of NMDA receptors, increased GABA-A receptor currents, and depressed AMP Aergic mEPSCs following a transient insertion of Ca- permeable AMPARs. We think the latter reflect altered glutamate receptor trafficking.

What is particularly interesting about the work from the perspective of other researchers?

I think the field at-large has appreciated the highly detailed and highly specific nature of our findings, which in general are in accord with a lot of other work done using more intact systems and less specific approaches. We have been a bit unique in the field because of our focus on understanding the function of surviving neurons rather than quantifying the extent of cell death produced by TBI. But that makes the work more stimulating, in my opinion.

What is particularly interesting about the work from the perspective of the public?

I think the work we do is so basic and the model so elegant that it can take some time to explain why we think the research is relevant. But I find that once I get across the idea that the forces we are applying to neurons “in a dish” are similar to those encountered by the brain of a person in an auto accident or a kid in a football game, or a soldier in Afghanistan who encountered an IED while driving his or her Humvee, I think the simplicity of the model, the basic nature of the information we can extract, and the possibility for scaling up the system to allow high throughput drug screening people get the point and find the work interesting. Plus, using our system as a “test bed” for new compounds or to test new hypotheses for TBI we can go forward to test these things in more intact models like fluid percussion or weight drop which are applied to whole animals.

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Modeling Kinetochores: When Form and Function Becomes Art, An Interview with Blerta Shtylla

1) How did you compose this image?

The image shows a rendition of the kinetochore attachment site and a kinetochore microtubule. When working on theoretical aspects of force generation at the kinetochore site, it has been useful to start by first drawing a simple diagram of the key working components of the system. This image arose due to attempts to visualize and integrate our physical interpretation of the site with the mathematical model results. I composed this image using Adobe Illustrator, since I was looking to include the raw images generated from our mathematical model for microtubule shapes with the rest of our drawn the components.

2) What prompted you to submit your image as cover art?

The geometry and arrangement of the kinetochore components in this image was visually striking to us, and so we thought it might make for a suitable cover art image of the Biophysical Journal.

3) How does this image reflect your scientific research?

This image is a good representative of the type of work that I engage in. We are interested in using mathematical modeling in order to interpret and understand the guiding principles of function and form for various
cellular components. The work on kinetochores is an excellent example of this, in that these sites are highly dynamic in their action, difficult to tease apart experimentally, but their shape and proper operation is
extremely important for precision during mitotic division.

4) Where do you see the artistry in your image? How did you come to see this?

I would say that the artistry would be in the composition of all the parts from our model results with known proteins in kinetochores. My main goal when working on this image was to draw a diagram of the site in a way that it vividly portrays to the viewer that the site is a dynamic living machine with moving components that can change shape.

5) Do you consider yourself an artist as well as a scientist? Any ideas or aspirations for your next science-as-art submission?

I would not call myself an artist most days, but I find that much of what we do requires a good degree of creativity. Many times, a great degree of creativity is needed in order to synthesize the intrinsic components of the systems that we model. Drawing diagrams, creating visualization tools helps us better understand the system we are modeling. In the end, it is the excitement of the science and mathematics that makes this even more fun and serves as a major form of inspiration.

7) Do you have a website where our readers can view your recent
research?

Yes: http://www.pages.pomona.edu\~bs044747.

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Senior producer Veronica Vaquer on the making of BPS TV

Imagine being hired by a foreign government to produce their local news. You’d have to learn a little of the country’s language and quickly assess what’s interesting and new to the locals. What’s common knowledge? What are their concerns and priorities? How do they communicate? Put another way, how do you capture issues important to an audience you’ve just met? This is Veronica Vaquer’s specialty. She was the senior producer of Biophysical Society TV at this year’s Annual Meeting, and, working for WebsEdge, she has produced television programs and web clips for diverse conferences- for medical and scientific societies and for police chiefs and fire chiefs. “We become a news channel for the conference attendees,” wrote Vaquer, “Often news or video production is trying to reach John Q. Public – but that’s not our goal — we want to have a more elevated discussion … about the topics at the Meeting.”

To produce BPS TV, Veronica worked with a small crew- editor, cameraman, logistics person, and a former L.A. TV reporter who conducted the interviews during the meeting. Six weeks to 2 months before the conference, they traveled to universities to shoot footage highlighting relevant research centers and technology. The clips produced from these trips were broadcast on TVs around the Moscone Center during the meeting. After the meeting, the clips become tools for the universities to advertise their strengths to funding agencies and prospective students. Once at the meeting, Vaquer and her team produced interviews with scientists and, each day, a one-hour newscast covering interesting events at the conference. You might have seen the interviews happening by the entrance of the exhibition hall.

For Vaquer, producing Conference TV is an opportunity to help people and professional societies get exposure for their work and tell their stories. Before working for WebsEdge, Vaquer worked for 10 years in local news, where reporting is intended to be disinterested. Here, Vaquer enjoys being able to help attendees articulate their thoughts in compelling videos. That can mean, in our case, creating videos that celebrate crystallography or highlight a symposium. At many conferences, there is also a big concern simmering under the surface of the main business. Making a video with Professor Steven Block of Stanford revealed the depth of the research funding crisis to Vaquer. So she drew out the theme from different perspectives over the rest of the conference in videos now available to everyone online.

Next time you’re at a conference make sure to look your best, you never know when you might be on TV!

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Restaurant-Style Review of Biophysical Society 2014

It’s been a while since I wrote a restaurant review and given all the great food I had in San Francisco, I’m inspired to present my final thoughts on this year’s meeting a la carte style….take what you like.

Science: The science was obviously the best part of the meeting. I enjoyed all the sessions I went to, though it was unfortunate that the East Coast storms prevented some of the speakers from attending the meeting. The big talks from Carlos Bustamante, Steven Chu, and the Award winners were all very interesting. The poster sessions were really well organized and made it easy to browse by your topic of interest.

Social: I was highly amused and slightly shocked at the post-National Lecture reception and dance. I guess those biophysics professors have got some moves! The ice cream and wine probably inspired people to rock out a little to live band as well. It was highly entertaining all around. The one thing I would like to see different next year is for the dinner meetups to start after the talks have concluded. I would have loved to go eat with some attendees but I wasn’t able to make it before the session ended. Some sort of lunch socializing (perhaps with a food order?) would have been awesome as well.

The Venue: I have always liked the Moscone Center area in terms of ease of transportation, nearby food, and the lovely Yerba Buena gardens right next door. I’m glad the meeting was held here and I hope everyone had a chance to explore the surroundings. Next year should be great as well with the Baltimore Convention Center sitting next to the fabulous inner harbor.

The Sides: I loved the Quartzy networking cards that made it really easy to keep track of the posters you visited and the people that you talked to. I will have to present next time just so I can get a few of my own. On the other hand, the phone app for the meeting could definitely use a few tweaks. The extra features, like the check-ins and messaging, were nice but the main purpose of the app is to make it easier to plan your day. It was a little user-unfriendly when it came to scheduling sessions or simply figuring out what room a talk was in.

Exhibit Hall: This part is probably a little biased because I got a good amount of swag (and candy!) from all the vendors. The photo contest and daily trivia were great add-ons as well, and I connected with plenty of aspiring people at the Graduate Institutions Fair. I wonder if there are plans to expand the variety of side activities for next year. It would be enjoyable to have a science communication contest of some sort such as the ever-growing three minute thesis competition.

Overall 5/5 Stars: It was a really good time and I enjoyed sharing it with all of you on the blog and via Twitter. I hope to do it again next year in Charm City!

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