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Feature

Protein Folding: Theory Meets Disease
Philip Hunter | Sep 7, 2003 | 10+ min read
Protein folding raises some of biology's greatest theoretical challenges. It also lies at the root of many diseases. For example, the fundamental question of whether a protein's final tertiary conformation, sometimes called the native state, can be predicted from its primary amino acid sequence is also of vital importance in understanding the protein's potential capacity to form disease-inducing aggregates. MISS A FOLD, PROMPT A DISEASE Here's a list of protein folding-related disease catego

Editorial

Taking the Pulse of Scientific Societies
Taking the Pulse of Scientific Societies
Scientific societies are an essential part of the research landscape. Almost all of us are members of one or more of them, and we have numerous reasons for joining. When I was a PhD student, I joined the British Society for Immunology, in part for the sense of belonging. I was eager to consider myself an immunologist; getting the badge of membership was a small but pleasurable step. My more pragmatic next-door neighbor, Steve, is a member of the American Association for the Advancement of Sci

Opinion

Improving the Postdoctoral Experience
Improving the Postdoctoral Experience
Improving the Postdoctoral Experience Ned Shaw Editor's note: Responding to readers' concerns about treatment of postdoctoral fellows in US academic life science labs, The Scientist invited the National Postdoctoral Association to participate in an online discussion with science policy leaders. Attendees included Rita Colwell, director of the National Science Foundation; economist Richard Freeman, Harvard University; Michael Gottesman, deputy director for Intramural Research, National Insti

Letter

Thanks from Iraq
Thanks from Iraq
Thanks from Iraq I am a final-year resident in pathology at Al-Zahrawi Teaching Hospital in Mosul, Iraq. I read your article in The Scientist1 (sent to me electronically by one of your subscribers). I thought it was very kind of you to rally your readers and the scientific community all around the world to help us, your colleagues in Iraq! We have indeed suffered and for a long time, not only from the UN sanctions, but also (and arguably more) from the underinvestment in education and scie
Saluting Self-Testers
Saluting Self-Testers
Saluting Self-Testers I found the article "Heal Thyself or Die Trying"1 particularly interesting because my father, Richard K. Bernstein, MD, developed blood glucose while self-monitoring for diabetes almost 30 years ago. A Type-1 diabetic from age 12, Dr. Bernstein was beginning to suffer from diabetic complications in his 30's. Using a cumbersome, first-generation blood glucose monitoring device available only to hospital emergency rooms (to distinguish comatose diabetics from drunks), h
Technicians Strike Back
Technicians Strike Back
Technicians Strike Back Thank you for your editorial of June 30.1 I am one of those research technicians you speak of, having gotten into the business 30 years ago, a refugee from a still very hostile climate in grad school (for women) with no clear job prospects at the other end and college debts. In my first years I was trained and abused by the best: the older faculty all had worked with Nobel laureates and two of the younger ones got the prize themselves. Since then, I have seen bad s
Ciao, Scienziati
Ciao, Scienziati
Ciao, Scienziati I am actually one of those "returning Italian scientists."1 I studied in the US for six years, from 1996 to 2002. I took my PhD in molecular cellular and developmental biology at Yale University and then decided to come back to work in Italy, thanks to this "Rientro dei Cervelli" program. I was given a stipend for three years (although not comparable to European standards), some money for research expenses, and a lab where I could work (in la Sapienza University, in Rome).
Y Not
Y Not
Y Not I think Ricki Lewis was trying to pull a fast one in her article "Y envy."1 I searched all of GenBank and couldn't find any mention of the P2E or RIF genes. I did find transient mention of an activator of male aggression (Ber). There's also an apparent silencing (post-transcriptional) of any "common sense" loci upon acquisition of PhD. The sad tragedy is that only female scientists will use the info from the Human Genome Project, as we guys don't use maps anyway. Thanks, Ricki! Now I
Nano Nano
Nano Nano
Nano Nano Congratulations on an excellent piece on nanoscience by Jeffrey M. Perkel in your July 28 issue.1 He rigorously covers much ground in little space; my only cavil is that, though writing in a bioscience journal, Mr. Perkel did not toot his (and your) own horn. Bioscience is a major reason behind current nanoscience's progress. The life sciences have been dealing with nanoscale objects and effects since their inception; the main difference now is that atoms and molecules can be ima
Down Under-represented
Down Under-represented
Down Under-represented I just wanted to make one comment regarding your surveys and information gathering: I think it is important that when discussing employment issues, lab politics, or general science issues, you should remember that quality science is generated from places other than the Northern hemisphere. That is, there are other thriving, first-world economies that are underrepresented in your discussions (e.g., Australia). Given that many 'Southern' scientists have the option of e
Where the Buffalos 'Ome
Where the Buffalos 'Ome
Where the Buffalos 'Ome Thomas Mennella1 has noted the ever-increasing use of "ome" as a suffix. He did not indicate that many people believe that a popular song begins, "'Ome, 'ome on the range." Moreover, as a young student he is unaware of the approaching omic doom. Many seniors experience this final indignity--the old folk's 'ome. Ronald Bentley Professor Emeritus University of Pittsburgh Pittsburgh, Pa. Rbentley+@pitt.edu 1. T. Mennella, "The out-of-hand omnipresent ome," The Scienti

Frontlines

Birds of a Feather, Banking Together
Birds of a Feather, Banking Together
Frontlines | Birds of a Feather, Banking Together More than fluff makes a feather. Tucked away in its vane and shaft is a surprising amount of valuable data. Thanks to recent technology breakthroughs, researchers can glean a lot of information about a bird's diet, mating behavior, and migratory habits by merely examining its plumage. "With improved PCR-based genetics, stable isotope analysis, and trace element fingerprinting, feathers have become a great research tool," says Keith Hobson o
Open Wide and Say
Open Wide and Say
Frontlines | Open Wide and Say "Ribbit" Some frogs may be croaking before they go 'a courting. Scientists working with students in Acadia National Park in Maine have observed plenty of dead tadpoles among the preserve's vast wetlands. But it's impossible to know whether the death rates are unusually high--the park's 47,633 acres span two islands and a peninsula--or whether some species are dying at higher rates than others, says Aram Calhoun, assistant professor of wetlands ecology, Unive

Snapshot

Counting the Ways of Keeping Up With It All
Counting the Ways of Keeping Up With It All
Click for larger version of survey graph (27K) A survey of 314 of our readers provides a picture of their science-reading habits. The majority, 56%, spends more than three hours per week reading primary research articles in print and online, and 10% read more than 10 hours per week. We asked respondents which multidisciplinary journals they read frequently. Naturally, The Scientist came out on top - these are readers of The Scientist after all - with 80% reading or skimming more than half t

Foundations

Little Green Bacteria
Little Green Bacteria
Foundations | Little Green Bacteria Click for larger version of notes (68K) When I first heard Paul Brehm [then at Tufts University] mention green fluorescent protein at a seminar in the late 1980s, I got excited; I knew it had the potential to be an expression marker. I talked with Doug Prasher, who was trying to isolate a gfp cDNA, and we promised to keep in touch. But we lost track of each other after I married and went to do my sabbatical at my wife's university. In September 1992, I

First Person

Mark B. McClellan
Mark B. McClellan
First Person | Mark B. McClellan Courtesy of FDA Mark B. McClellan, the baby-faced, dual-degreed head of the Food and Drug Administration, is rarely the prince when he plays dress-up with his twin 4 1/2-year-old daughters. McClellan, the 40-year-old former Stanford economist and internist, is generally the ogre. Or the dinosaur. He takes his servile status in stride. "Princes are not an integral part of these stories," says McClellan, who was weaned on Texas politics. "There are weddings,

Science Seen

Incredible Voyager
Incredible Voyager
Science Seen | Incredible Voyager Courtesy of Parmabase  Tired of boring database interfaces? This might resemble just another cellular diagram, but it's actually a navigation device for Pharmabase, a physiology and pharmacology database (www.pharmabase.org). Although still under construction, users eventually will be able to click on any organelle and go directly to a site that will provide its relevant pharmacological properties. function sendData() { document.frm.pathName.value =

Off The Cuff

Science Sybils
Science Sybils
Off The Cuff | Science Sybils What journal and article titles will PubMed list in 2053? "Nano-Molbiol Techniques." G.R. Kantharaj, Don Bosco College, Bangalore, India "Human genes responsible for immortality." Hari Har Joshi, Tribhuvan University, Teaching Hospital, Kathmandu "First functional interface between a (vertebrate) brain and a micoprocessor." Stephan Schuster, Max-Planck Institute, Germany "The rapid generation of speeds greater than the speed of light in space travel."

5-Prime

Getting Tidy: Protein Folding
Getting Tidy: Protein Folding
5-Prime | Getting Tidy: Protein Folding What is protein folding? It is the process by which proteins acquire their functional, preordained, three-dimensional structure after they emerge, as linear polymers of amino acids, from the ribosome. Who discovered it? In the 1940s, Linus Pauling and Robert Corey elucidated the a-helix and the b-sheet, which are considered the two fundamental building blocks of all protein secondary structures. In the early 1970s, Christian Anfinsen showed that a

Research

RAMPs on Trial
RAMPs on Trial
Click to view a PDF of antimicrobial peptides in various living organisms (141K) Living organisms produce a vast array of germ-killing peptides as their first-line of defense against infection. Scientists began to learn of these molecules in the 1980s from studies by Hans Boman and colleagues at the University of Stockholm, Sweden. They found that silkworm moth pupae secrete certain peptides that destroy invading bacteria. These controversial peptides (see Antibiotic Arms Race Heats Up) are
Antibiotics Arms Race Heats Up
Antibiotics Arms Race Heats Up
© 2002 Wiley Periodicals, Inc.  AT DEATH'S DOOR: Negatively stained Pseu-domonas aeruginosa (A) untreated, (B) treated with amphipathic a helical lytic peptide dia-stereomer (containing both L- and D-amino acids), and (C) treated with with the all L-amino acid peptide. All were treated at 60% of their minimal inhibitory concentration (MIC). At or above the MIC, significant lysis occurs (not shown). (Y. Shai, "Mode of action of membrane active antimicrobial peptides," Biopolymers (Petp
Steroid Action Gets a Rewrite
Steroid Action Gets a Rewrite
A TENTATIVE INTERPRETATION:Genomic actions of steroid hormones...Click for larger version (42K) Molecular biologists are rewriting the textbook explanation of steroid action. For 40 years, evidence has accumulated that some of the hormonally induced effects seemed too rapid for the classic model, in which steroids activate cytosolic receptors to modulate transcription. This evidence casts doubt on the so-called genomic pathway as the sole mode of steroid action. Increasing research now highl

Hot Paper

Cancer's Other Conduit
Cancer's Other Conduit
Courtesy of Elsevier  DEADLY SPREAD: A: an insulinoma (Ins) in a Rip1Tag2 transgenic mouse. LYVE-1 immunohistochemistry demonstrates the presence of lymphatic vessels in connective tissue, but not near islets of Langerhans. B: Rip1Tag2 mice were crossed with mice which overexpress VEGF-C in pancreatic b-cells. C: An insulinoma cell breaks through a lymphatic vessel. D: An intralymphatic tumor cell mass forms. E: In a lymph node, lymphocytes (L) are surrounded by tumor cells (T). F: Immunof

Research Briefs

Eating for Two, or an Entire Lineage; Serine at the Start of Life; Interdisciplinary Research
Eating for Two, or an Entire Lineage; Serine at the Start of Life; Interdisciplinary Research
Research Briefs Eating for Two, or an Entire Lineage; Serine at the Start of Life; Interdisciplinary Research Eating for Two, or an Entire Lineage Courtesy of Randy Jirtle Duke University researchers give a new twist to the old adage, "You are what you eat." By feeding female agouti (Avy) mice methyl-rich supplements such as folic acid and vitamin B12, Randy Jirtle and Robert Waterland reduced agouti gene expression in their offspring. This change, caused by direct methylation of a transp

Technology Front Page

Tracking and Archiving PDFs; Clasp that Cover Slip; Electrifying Gene Therapy
Tracking and Archiving PDFs; Clasp that Cover Slip; Electrifying Gene Therapy
Front Page Tracking and Archiving PDFs; Clasp that Cover Slip; Electrifying Gene Therapy SOFTWARE WATCH | Tracking and Archiving PDFs When Martin Kucej, a molecular biology postdoctoral fellow at Comenius University in Bratislava, Slovakia, couldn't find a journal article on his shelf of documents, he decided to digitize all the documents pertaining to his research project. But he could not find a program that would allow him to do that and share the library with his laboratory colleagues,

Technology Profile

Tissue Microarrays Coming of Age
Tissue Microarrays Coming of Age
Courtesy of Marisa Dolled-Filhart, Robert L. Camp, and David L. Rimm  CORE TECHNOLOGY: Images of a breast cancer tissue microarray core immunofluorescently stained with (clockwise from top left) a rabbit pan-cytokeratin antibody, an Estrogen Receptor antibody, and DAPI, allowing for differential fluorescent tagging of each. If there's anyone who can appreciate tissue microarrays, it's histology technician Sabina Magedson. Having worked in a pathology laboratory at M.D. Anderson Cancer Ce
Gene Transfer Technologies
Gene Transfer Technologies
Courtesy of Qbiogene  GOT LACTOSE? 3T3 cells expressing b-galactosidase (which converts lactose into glucose and galactose) after transfection with Qbiogene's jetPEI reagent. Laboratories are loading mammalian cells and tissues with exogenous DNA more routinely and more successfully than ever before. The means available to deliver the DNA--lipofection, transduction, electroporation, and so on--seem to be increasing at a staggering rate, whether measured in terms of published protocols, c

Technology

ChIP-ing Away at a Proteomics Bottleneck
ChIP-ing Away at a Proteomics Bottleneck
Courtesy of Andrew Gooley, Proteome Systems Among proteomics techniques, protein microarrays may be getting a lot of buzz these days, but two-dimensional gels still do most of the work. That's because protein arrays present a number of technical challenges that have limited their implementation.1 Proteins vary wildly in stability, solubility, viscosity, and ease of synthesis, for instance. And, the in vitro translated proteins generally used to construct protein biochips often lack the wide d
Speeding up Cell Imaging
Speeding up Cell Imaging
Courtesy of Q3DM Drug discovery companies frequently use high-throughput cell imaging systems to increase the efficiency of secondary screening of drug candidates, and the number of available systems has grown in recent months to meet this demand. Among the competitors is San Diego-based Q3DM's EIDAQ 100 system, the product of a combination of patented technologies that, according to the company, improve throughput and image fidelity over conventional automated cell-imaging systems. The EIDA
The Great Chip Chase
The Great Chip Chase
Courtesy of Agilent Technologies With last year's complete sequencing of the human genome, a number of manufacturers raced to produce the first series of human genome microarrays, which were actually sets of two or more chips or slides. The next generation of human whole-genome arrays places the entire genome on a single chip, allowing scientists to observe gene expression profiles on one surface and under uniform experimental conditions, minimizing sample use and labor. "Now that the human g

Profession Front Page

When Postdocs Change Their Minds; Keys to Computing; Researchers Find Key to Long Life
When Postdocs Change Their Minds; Keys to Computing; Researchers Find Key to Long Life
TIP TROVE | When Postdocs Change Their Minds Courtesy of Gordon Keller If you're not excited about what you're doing, you're just not going to do it well. Mentors should encourage independent thinking. If postdocs want to change the direction of their projects, or explore new avenues, I certainly encourage it. However, if you find that you've chosen an area of research that doesn't interest you, I would advise you to think carefully about your choices ... and if you are absolutely certain y

Profession

Stem Cell Pioneer
Stem Cell Pioneer
Stem Cell Pioneer
It's a day neurobiologist Oliver Bruestle remembers well. He dropped the letter into the mailbox in August, two years ago. Addressed to the German Research Society, Germany's main funding organization for biomedical research, the envelope contained a grant proposal for work on human embryonic stem cells (ESCs), to be imported from Israel. "I knew this would generate some waves," relates Bruestle, "but I definitely did not count on a tempest of these proportions." His proposal, routine by mos
The Science of Entertainment
The Science of Entertainment
Courtesy of Edgeworx/A. Cross/J. Dunn for NOVA  SCIENTIST STAR Brian Greene uses special effects to initiate readers in string theory ABC Television turned the best-selling book Dinotopia, about a fantasy world where dinosaurs talk and play ping-pong, into a miniseries. The network celebrated by hosting a party at, of all places, the faculty club of the California Institute of Technology. The event featured network executives, celebrities, and an animatronic Tyrannosaurus rex. At least on
Graph with Gusto
Graph with Gusto
The charge that scientists are bad writers is hardly an aphorism. Just read any scientific paper outside of your field and you'll quickly be lost in a jungle of jargon and poorly explained concepts. Yet most scientists struggle mightily with wordsmithing, some going so far as to hire consultants, because they understand the importance of a well-written manuscript. The same does not always apply to illustrations, a catchall term for all graphical representations of scientific data, including d
Building La Dolce Vita with Science
Building La Dolce Vita with Science
Research collaboration between the National Institutes of Health and the Istituto Superiore di Sanità (ISS) began with the signing of a Letter of Intent at the end of July. This institutional agreement confirms a Memorandum of Understanding for greater US-Italian cooperation in health and medical science signed on April 1. The partnership is designed to promote research areas of mutual interest, including cancer, cardiovascular disease, pulmonary disease, women's health, and neuroscien

Science Rules

New EU Money for Research
New EU Money for Research
File Photo The European Molecular Biology Organization (EMBO) is setting up a grant program to fund ¤30 million each year for outstanding research in molecular biology. The program may be of particular interest to scientists from smaller countries and to those who are working in research that is difficult to fund (such as work with genetically modified plants). This scheme may make science more competitive because researchers will vie for grants with peers from all over Europe, rather th

Postdoc Talk

Making Postdocs Part of Your Team
Making Postdocs Part of Your Team
Courtesy of Carol L. Manahan Recently, I attended a symposium called "Catalyzing Team Science," which gathered representatives from the institutes of the National Institutes of Health; it was sponsored by the Bioengineering Consortium (BECON), a senior interagency committee that focuses on bioengineering efforts at the NIH. This was the first time that BECON has invited a postdoctoral fellow to such a symposium (www.becon1.nih.gov/symposium2003.htm). In contrast to other areas of science, suc

How I Got This Job

Risk the Unpopular and Marry Talent
Risk the Unpopular and Marry Talent
Courtesy of Robert Blanchard Early Indications: As an undergraduate I was attracted to experimental psychology, because it seemed to provide a scientific approach to understanding animal and human behavior. Pivotal Papers: There were two; one in each area that has turned out to be a focus of the lab. "Crouching as an Index of Fear" (J Comp Physiol Psychol, 67:370-5, 1969) raised the heretical specter of a powerful unconditioned fear response and also provided a neat demonstration of rapid a

Turning Points

Piercing the BiotechBarrier
Piercing the BiotechBarrier
File Photo How can I break into the biotech or pharmaceutical industry? That's a question many of my readers ask. Michael Ferguson, senior manager of clinical development for Memphis, Tenn.-based Medtronic Sofamor Danek, offers insights for people who wish to take the industry path. Two years into his PhD studies in applied physiology at the University of Florida, Ferguson decided he wanted to join a biotechnology company or a clinical setting. His first step was to work for a small firm dur

Closing Bell

Power Lost, Power Gained
Power Lost, Power Gained
My alarm clock was blinking an erroneous time, but I ignored it; I had just taken a much-appreciated nap, and I needed to get back to a yeast cell biology conference at Cold Spring Harbor Laboratory. I was staying 10 miles away at a Vincentian seminary that housed students like me. My fan was running, and my cellular phone recharger was pulsing red. I had no idea that the power was coming from a backup generator. I was probably one of a few people of about 50 million, from Canada to New Jers
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