September 2004

The article on theranostics1 was lucid, to the point, and informative. As a diagnostic pathologist I am dealing with interpretation of new tests that determine the candidacy of patients for specific targeted therapies. The immuno-histochemical tests (i.e., Herceptest, EGFR PharmDX, and c-Kit) are not much of a problem to perform and interpret. The tissue-based molecular assays, on the other hand, not only require sufficient sample sizes (as you pointed out), but also require special handling to

A recent feature article in Nature examined the scientific impact of nations using the metrics of total publications and citations.1 For decision-making purposes, the article appears to be misleading, because critical and noncritical technologies, with high-tech and low-tech components, are country-aggregated in these numbers. Most important for potential users are critical technologies that impact strongly defense and civilian commerce.For example, in the 1997–2001 time frame, China is li

The "How it Works" article on fluorescence activated cell sorting1 incorrectly suggests that Len Herzenberg developed the first fluorescence-activated cell sorter. In fact it was developed by Mack Fulwyler, Marv Van Dilla, John Steinkamp, and James Coulter.2 Fulwyler and colleagues adapted the principle of ink-jet droplet deflection developed by Richard Sweet to sort cells.3At roughly the same time, Lew Kamentsky developed a fluidic-switch based cell sorter.4 Both Fulwyler and Kamentsky's sorter

Imagine giving captopril, a blood pressure-lowering agent, to patients infected with anthrax, many of whom may have extremely low blood pressures because they're in shock or on the verge of it. Sounds crazy, right? But that's just what some clinicians suggested in the wake of the 2001 anthrax letters, based on animal studies showing that captopril could inhibit the lethal anthrax toxin.For a more recent example of how enthusiasm for important findings in basic science can often get the best of c

Last month, two writers from The Scientist and about 350 other reporters were among 1,800 participants at the inaugural EuroScience Open Forum in Stockholm. The meeting was billed as "the first pan-European science meeting ever," and included sessions on a familiar mix of diseases, planets, and dinosaur bones.Unfortunately for news hounds, the EuroScience meeting, like the annual American Association for the Advancement of Science (AAAS) conference on which it is modeling itself, was an exercise

It's the beginning of a new television season, which must mean it's time for the next in a line of television series glorifying the fast-paced, glamorous lives of scientists. NBC has brought us Medical Investigation, in which public-health specialists take to the streets (and the skies) to sleuth out the source of unexplained illnesses. In the series premiere aired earlier this month, the crack team of MDs and PhDs descend upon New York City to figure out why a dozen people have fallen ill and a

© Christopher Zacharow/Images.comGene therapy's heady days of introducing the gene for adenosine deaminase into immune cells to treat a life-threatening congenital defect, as was done in the first gene therapy trial in 1990, have given way to an atmosphere of caution. In 1999, Jesse Gelsinger died of multiple organ failure four days after receiving adenovirus-based therapy for a rare liver disorder. In 2002, a child developed leukemia after receiving retroviral therapy for X-linked severe c

Erica P. JohnsonA biomolecular 'piston' derived from viral peptides should respond to changes in pH.Engineers expect that tomorrow's nanomachines – biomolecular devices that might patrol cells, repair genes, scour out infections, and haul away debris – will be powered by nature's own motors: the proteins kinesin, myosin, and dynein, which turn adenosine triphosphate (ATP) into fuel and move loads along microtubular tracks of actin and tubulin.It makes sense to use these off-the-shelf

THE DEAMINATOR:© 2004 Cell PressTwo proposed models of activation-induced cytidine deaminase activity. At left AID edits RNA allowing translation of a functional DNA endonuclease that works on both variable (V) and switch (S) region DNA. This results in somatic hypermutation (SHM) through nicks and error prone repair and class switch recombination (CSR) through staggered nicks and nonhomologous DNA end-joining (NHEJ). An alternative model proposes that AID modifies DNA directly and that CSR

BIOFACTORIES:© 2003 Nature Publishing GroupAbove is a depiction of the genetic network engineered into Escherichia coli for production of amorphadiene via the DXP or mevalonate isoprenoid pathway. The black triangles represent the PLAC promoter. Genes isolated from Saccharomyces cerevisiae, E. coli, and Haematococcus pluvialis were used to construct the network. (From V.J.J. Martin et al., Nat Biotechnol, 21: 796–802, 2003.)Synthetic biology is a new discipline based on the expectatio

In the world of fluorescent labels, organic dyes are out, and quantum dots (QDs) are in. These nanosize crystals of semiconducting material (typically CdSe) sport a broad excitation profile, strong fluorescence, enviable photostability, and narrow, size-dependent emission spectra. QDs are ideally suited for most multiplexed fluorescence applications, but not for fluorescence resonance energy transfer (FRET).Because different QDs will fluoresce under the same excitation wavelength, they cannot fu

These papers were selected from multiple disciplines from the Faculty of 1000, a Web-based literature awareness tool http://www.facultyof1000.comN. Gupta-Rossi et al., "Monoubiquitination and endocytosis direct γ-secretase cleavage of activated Notch receptor," J Cell Biol, 166:73–83, July 5, 2004.This paper is important because it shows that the Notch receptor must be monoubiquitinated and endocytosed before it can be cleaved by presenilin/γ-secretase, a key step in Notch activa

Courtesy of Andrew Baker, Wildlife Conservation SocietyRutgers University scientists have identified a physiological mechanism behind the bleaching that has affected coral reefs worldwide over the past three decades. Bleaching follows a rise in sea temperature, and it involves the ejection by coral polyps of symbiotic, photosynthetic algae from their tissues. Led by Paul Falkowski, professor of biological oceanography, the study finds that the melting of the fatty acid-based thylakoid membrane o

THE POWER OF PHYLOGENY:Studies of the β-globin gene promoter illustrate the power of phylogenetic footprinting, and the importance of species choice in that analysis. (a) Transcription factor analysis of the human promoter without footprinting reveals numerous predictions, most of which are biologically irrelevant. (b) Comparison with the chicken promoter fails to detect conserved sites, but comparison with the mouse promoter does (c), including a documented GATA-binding site (boxed). (d) C

Courtesy of C.C. ChengBulged structures are crucial motifs in the recognition of DNA by nucleic acid-binding proteins, says Chien-Chung Cheng of Academia Sinica, Taipei, Taiwan. So, they're important as potential targets for antiviral drugs. They also are known to be intermediates in the process of frame-shift mutagenesis.But unlike RNA, says Cheng, "it has been difficult to obtain detailed structural information about DNA bulges, because they are relatively unstable." The most common detection

Courtesy of Stanford University Medical CenterUsing live cells arrayed on a chip, a Stanford University team has prototyped an implantable silicon wafer designed not only to improve sight in macular degeneration patients, but also to dispense drugs and collect fluid samples inside the body.1 The implant, now in development, will be nearly 2.5 cm in diameter, 10 microns thick, and honeycombed with hundreds of microchannels, which will dispense neurotransmitters either from onboard stores or a tin

Courtesy of Filippo RusconiWhile a graduate student, Filippo Rusconi couldn't come up with the money to pay for a Microsoft developer's license to continue work on his mass spectrometry program. So instead he rewrote the whole program in GNU/Linux. It turned out to be the best thing that happened to him, he says. "It allowed me to make the program a thousand times more powerful."The program, now called GNU polyxmass http://www.polyxmass.org is a complete software suite for mass spectrometrists t

The genomics revolution that reached its climax in 2000 owes its very existence to two men. The first is Frederick Sanger who in 1977 developed the method for DNA sequencing that now bears his name. The second is Leroy Hood, who (with colleagues Michael Hunkapiller and Lloyd Smith) in 1986 took Sanger's method and made it better.Sanger's enzymatic approach relies on specially modified reagents (2',3'-dideoxynucleotide triphosphates) whose incorporation into a growing DNA strand terminates the ex

© 2004 Society for NeuroscienceScientists at Carnegie Mellon University in Pittsburgh have created a transgenic mouse that will allow researchers to visualize patterns of activity directly in individual neurons in vivo.1 To create the animals, Alison Barth and colleagues coupled the c-fos promoter, which is typically activated during neural activity, to a green fluorescent protein (GFP) marker. "By coupling c-fos activation to the expression of GFP, I could now see cells that were specifica

Combining the visual power of standard immunostaining with the broad scope of the protein array, the Staining Antibody Array from Worcester, Mass.-based Hypromatrix http://www.hypromatrix.com allows researchers to stain different cells in the same sample for dozens of proteins simultaneously. The array, containing about 100 antibodies fixed on a nitrocellulose membrane, is incubated with the tissue to be stained. When the array is removed, the antibodies remain bound to proteins in the tissue an

Courtesy of BD Biosciences ClontechPalo Alto, Calif.-based BD Biosciences-Clontech's Nucleo-Spin DNA extraction systems received a design update – this spring, making the popular kits more user-friendly and cost-efficient for labs with both high- and low-throughput applications http://www.clontech.com."We've changed the format of the eight-well strips so they look and handle identical to the 96-well plate," says product manager Linnea Hager. The eight-well strips and 96-well plates are now

Though recognized as prime drug targets, membrane proteins largely remain terra incognito for structural biologists because they are so difficult to express in eukaryotic-cells. Michael Mendez of Gryffin Consulting, a genetic engineering firm, explains that the main difficulty in expressing membrane proteins is cell toxicity: Overexpressed proteins that cannot be processed in the endoplasmic reticulum (ER) initiate apoptosis, killing the cell. Altering the processing mechanism would prevent cell

Courtesy of Jong-Hoon Kim & Ron McKay, NIHA human embryonic stem cell starter panel that allows for the in vitro expansion of human ESCs is now available from Minneapolis-based R&D Systems http://www.rndsystems.com. The kit contains human FGF basic protein, antibodies to Oct-3/4, stage-specific embryonic antigen (SSEA)-4, and alkaline phosphatase to monitor the cells' differentiation status."The biggest plus as well as the biggest problem with ESCs is that they are multipotential and can

Applied Biosystems www.appliedbiosystems.com, based in Foster City, Calif., has introduced a new family of reagents for multiplexed LC/MS experiments. The iTRAQ reagents enable comparison of protein expression in multiple samples, such as those of normal, diseased, and drug-treated states, and have the ability to detect posttranslational modifications, the company claims. The company has also released Pro QUANT software for automated analysis of LC/MS data collected using the reagents.ICAT reage

THE SANGER METHOD:Single-stranded DNA is mixed with a primer and split into four aliquots, each containing DNA polymerase, four deoxyribonucleotide triphos-phates and a replication terminator. Each reaction proceeds until a replication-terminating nucleotide is added. The mixtures are loaded into separate lanes of a gel and electrophoresis is used to for an illustration of a high-speed DNA sequencer.)What's happening in the DNA sequencing industry? After all, the human genome sequence is done an

Business and science can seem like two different worlds, and some scientists are now entering joint programs so they can work and speak fluently in both. A number of schools have launched joint PhD/MBA programs in recent years, including Cornell University, San Diego State University, University of California, San Diego, University of Rochester, NY, and Wake Forest University. Business-savvy scientists may give a company a competitive edge or may be the key to a successful startup.Joel Martin ea

Getty ImagesShannon Thomas was working on her PhD in organic chemistry at the University of California, Santa Cruz, when she came across a trade publication advertisement for a patent agent. "They wanted someone with good communication skills and technical expertise to assist and be a liaison with lawyers," she says. "It sparked my interest. I had no idea that kind of job existed."So during her final year of graduate school in 2002, Thomas took a course to prepare for the patent bar exam. She wa

Searching through US patent applications previously required a trip to the US Patent and Trademark Organization (USPTO) in Washington, DC, followed by a dig through mountains of files. Today, all it takes is an Internet connection http://www.uspto.gov/patft/index.html. All patent applications not covered by confidentiality laws, or about 90%, are now fully accessible online 18 months after being filed, the USPTO announced in August. This innovation will give inventors a much better sense of the

What is the role of the daily news operation of a magazine such as The Scientist? It's an important question that bears considering periodically. If we start with the magazine's motto, "The News Journal for the Life Scientist," we have somewhat of a guide as to what the editors think: The daily news service is dedicated to informing life scientists of the news of the day in policy and research, which leaves the print magazine you're reading now to reflect on larger trends.But some of the readers

A few weeks ago I spotted, in someone's trash, Isaac Asimov's science fiction classic, The Foundation Trilogy. Shortly after, I found the 1954 giant-ants-in-L.A. film, Them, in a discount store video bin. Garbage to some, these tales were once treasures to me, although I prefer science fiction more subtle than the formulaic doomsday scenarios of humanity succumbing to oversized or overabundant (a) birds, (b) mind-snatching seed pods, (c) blobs, and of course (d) ants. The humans always prevail.T

Once upon a time, just over a hundred years ago, a wizard addressed a large gathering of industrial and scientific leaders. Drawing on his 20/20 foresight, he described the powerful discoveries that could enrich the coming century. "Your current language is inadequate," he said. So he conjured visions of energy quantization, relativity theory, atomic and nuclear structure, quantum mechanics, and molecular biology to give some impressions of the sciences that might come. With mounting excitement,