December 2007

In 1985, as a professor of physiology at Tufts University School of Medicine, Lewis Cantley and his colleagues discovered the phosphoinositide 3-kinase (PI3K) pathway that determined much of his later career. Now, as a professor of systems biology at Harvard Medical School, Cantley continues to investigate PI3K, the biochemical pathways that regulate normal mammalian cell growth, and the defects that cause cell transformation. In "From Kinase to Cancer," he discusses how the past two

Marianne Emanuel By Anne Harding A nurse who cares for the whole person - body, and spirit. © Dustin FensterMacher | Wonderful Machine ARTICLE EXTRASThe DiseaseLiving with SchizophreniaRobin CunninghamA Very Expensive DiseaseSchizophrenia in ChildhoodMarianne Emanuel was ready to give up on nursing in 1991. At 37, she'd worked in numerous settings, including hospitals, intensive care units, and doctor's offices. "After

A Very Expensive DiseaseBy Anne HardingFlaws in the system add to the tens of billions spent on schizophrenia every year, but advocates say there's little will to invest in fixing it. ARTICLE EXTRASThe DiseaseLiving with SchizophreniaRobin CunninghamMarianne EmanuelSchizophrenia in ChildhoodWhen Janet Edelman's brother became ill with schizophrenia, she and her parents went through a period of mourning for what they - and the rest of the world - had lost. "My brother should have been a profess

var FO = { movie:"http://images.the-scientist.com/supplementary/flash/53924/53924.swf", width:"520", height:"410", majorversion:"8", build:"0", xi:"true"}; UFO.create(FO, "ufoDemo"); Passive immunization and West Nile Virus By Edyta Zielinska In 1999, officials reported the first cases of West Nile Virus (WNV) in North America in eight New York City patients. Baxter Healthcare scientist Thomas Kreil realized that sera from infected patients might prote

1 This diagnosis is often difficult to confirm, because it is quite common for children to have magical thinking or beliefs, and they often report auditory hallucinations that occur upon waking or sleeping (hypnagogia or hypnopompia, respectively). In addition, children may not be able to articulate their psychotic symptoms as clearly as adolescents or adults, thus making the diagnosis less clear-cut. So, too, can other symptoms mistakenly resemble psychosis, including idiosyncratic thi

Betting on Better Organs © 3D4medical.com Will you soon be able to buy your own bladder? By Alison McCook Related Articles 1 Patients are left with less tissue to function as intestine, which can complicate things even further. Some studies have also linked the procedure to a slightly higher risk of cancer. Performing this procedure in older adults, who have relatively fewer years left to develop complications, is one thing. But what

1While no one really knows what causes the GAD67 abnormalities - they might be due to variants in the gene for GAD67, problems with gene expression, or both - the ultimate cause may not really matter, says Lewis, since drugs might be able to regulate neuronal activity by targeting these downstream problems directly.His lab has discovered that GAD67 abnormalities affect only a subset of neurons: those that produce parvalbumin and somatostatin.2 Of note, these cells are also involved in certain ty

var FO = { movie:"http://images.the-scientist.com/supplementary/flash/53927/organ.swf", width:"550", height:"500", majorversion:"8", build:"0", xi:"true"}; UFO.create(FO, "ufoDemo"); Engineering an organ By Alison McCook How Tengion builds autologous bladders Please download the Adobe Flash Player to view this content: Related Articles Betting on better organs What it takes to make an organ

What it takes to make an organ By Alison McCook Related Articles Betting on better organs Engineering an organ Two years ago, the first employees of Tengion walked into a 2,800 square meter warehouse in southeastern Pennsylvania that was full to the brim with office furniture, rising up to a 12-meter ceiling, and said: We'll take it. They cleared everything out and started to fill the empty space with rooms and equipment to automate something that had

The problem with plants By Bob Grant Related Articles Cataloging Life The Barcoding Factory Hiding in plain sight Slideshow: Barcoding the world Back pocket barcoder? Animal barcoders are on a tear. Every day they inch closer to completing a library of CO1 sequences from the planet's birds, fishes, mammals, and invertebrates. But researchers hoping to barcode Earth's plants are in a different boat. "Animal people are well on their way," sa

Back pocket barcoder? By Bob Grant Related Articles Cataloging Life The Barcoding Factory Hiding in plain sight Slideshow: Barcoding the world The problem with plants It was 2003, and University of Guelph researcher Paul Hebert was taking heat from an audience of taxonomists and phylogeneticists at a Cold Spring Harbor Laboratory seminar for suggesting that they barcode Earth's inhabitants using the CO1 mitochondrial gene. University of Pennsy

var FO = { movie:"http://images.the-scientist.com/supplements/20071201/swf/infographic.swf", width:"520", height:"580", majorversion:"8", build:"0", xi:"true"}; UFO.create(FO, "ufoDemo"); 1 There are also consistent reductions in the size of the medial temporal lobe and the left neocortical superior temporal gyrus in patients with schizophrenia; those areas are responsible for declarative memory and auditory processing, respectively. Some studies have also found that the

Cataloging Life Can a single barcode of DNA record biodiversity and keep us safe from poisons? By Bob Grant Related Articles 1 for soil nematodes, barcoding's genesis lies in a 2003 paper in Proceedings of the Royal Society of London2 by Paul Hebert, a Canadian researcher who some call "the father DNA barcoding," and colleagues. In that paper, Hebert's team proposed a universal animal barcode: a segment of roughly 650 base pairs of the mitochondria

Out of Mind When I was a medical student in the mid-1990s, many of the newer generation antipsychotics used to treat schizophrenia, such as risperidone and olanzapine, were just coming on the market. My psychiatry rotation was at the famed Bellevue Hospital in New York, and half of the unit to which I was assigned was filled with patients in clinical trials of many of those drugs. In many cases, these were double-blinded, placebo controlled trials, but that was a bit of a f

var FO = { movie:"http://images.the-scientist.com/supplementary/flash/53904/53904.swf", width:"530", height:"550", majorversion:"8", build:"0", xi:"true"}; UFO.create(FO, "ufoDemo"); Barcoding the world From Canada to Taiwan, barcoding is a truly global phenomenon. Researchers are conducting barcoding projects that aim to catalog Earth's trees, birds, and fish. Staff writer Bob Grant traveled to Taipei to attend the Second International Barcode of Life Conferen

var FO = { movie:"http://images.the-scientist.com/supplementary/flash/53903/plainsight.swf", width:"425", height:"575", majorversion:"8", build:"0", xi:"true"}; UFO.create(FO, "ufoDemo"); Hiding in Plain Sight DNA barcoding can help uncover new species that are morphologically indistinguishable from closely related species. In some cases, these look-alikes were misidentified for decades. Here are some examples of species whose barcodes differ enough to be co

Neurotrailblazer By Melinda Wenner Martha Shenton is pushing imaging boundaries in order to understand the schizophrenic brain © 2007 Jared Leeds ARTICLE EXTRAS The Etiology Molecular Mysteries Gazing Downstream Seeing Schizophrenia Pregnancy, Chromosomes, and Receptors Martha Shenton is what you might call a maverick. As the director of Brigham and Women's Hospital's Psychiatry Neuroimaging Laboratory in Boston, s

Following the PI 3-kinase pathway By Lewis Cantley Phosphatidylinositol 3-kinase (PI 3K) acts upstream of myriad cellular pathways, including those that regulate protein synthesis and tumorigenesis. In this example, PI 3K phosphorylates the lipid PI -4,5-P2 to PI -3,4,5- P3, also known as PIP 3. PIP 3 binds to serine/threonine kinase (AKT) and recruits it to the membrane where PDK1 phosphorylates the kinase and sets it into action. Among a number of targets, AKT phosphor

The Treatments ARTICLE EXTRAS A Troubled History First-Generation Antipsychotic Drugs The Atypical Atypical? The next generation? The Lessons of CATIE Second-Generation Antipsychotic Drugs Beyond Drugs Nonmedication Therapies When you add up the direct costs of treating patients with schizophrenia, it is a staggering number: $22 billion in the United States alone. As effective as many of them are, antipsychotic drugs are costly, and many have signific

var FO = { movie:"http://images.the-scientist.com/supplementary/flash/53942/pip.swf", width:"520", height:"780", majorversion:"8", build:"0", xi:"true"}; UFO.create(FO, "ufoDemo"); Putting the P in PIP by Lewis Cantley Click on the enzyme names or on the the arrows to follow the PIP pathway. Please download the Adobe Flash Player to view this content: Related Articles From Kinase to Cancer Following the PI 3-kinase

Watching Wolfson In 12 years, the UK institute has produced 600 papers, 6 spin-offs, and 31 patents. Does this mean its unique approach is working? By Stephen Pincock Related Articles 1 and new details on how a nitric oxide-cGMP-dependent pathway controls mitochondrial biogenesis and the body's energy balance.2,3 The standout feature of the institute is the way it has managed to achieve genuine interaction among researchers of different disciplines,

A Troubled History Antipsychotics are effective, but carry significant side effects and cost. What's on the horizon? ARTICLE EXTRAS The Treatments First-Generation Antipsychotic Drugs The Atypical Atypical? The next generation? The Lessons of CATIE Second-Generation Antipsychotic Drugs Beyond Drugs Nonmedication Therapies Soon after antipsychotics entered the market in the 1950s, policymakers were so impressed with their benefits th

The Atypical Atypical? By Jonathan Scheff A new class of antipsychotics aims at NMDA receptors ARTICLE EXTRAS The Treatments A Troubled History First-Generation Antipsychotic Drugs The next generation? The Lessons of CATIE Second-Generation Antipsychotic Drugs Beyond Drugs Nonmedication Therapies Until the 1980s, researchers didn't consider the excitatory amino acid N-methyl-D-aspartate (NMDA) to be a receptor in mammalian brains. That began to c

First-Generation Antipsychotic Drugs By Jonathan Scheff This table lists selected first-generation antipsychotic drugs. For a table of atypical agents, click here. For a table of the next generation of medications, click here. Drug Brand name(Manufacturer) Approval date Indications Mechanism Cost per 30-day supply* Contraindications/Adverse reactions Injection availability Other data Prochlorperazine October 1956 Seve

The next generation? ARTICLE EXTRAS The Treatments A Troubled History First-Generation Antipsychotic Drugs The Atypical Atypical? The Lessons of CATIE Second-Generation Antipsychotic Drugs Beyond Drugs Nonmedication Therapies This table lists a selection of antipsychotics in the pipeline. For a story on a new class of drugs some are referring to as the "atypical atypicals," click here. For a table of first-generation drugs, click here. For a table of a

The Lessons of CATIE By Jonathan Scheff The landmark study found that older antipsychotics were just as effective as newer ones. Is anyone listening? ARTICLE EXTRAS The Treatments A Troubled History First-Generation Antipsychotic Drugs The Atypical Atypical? The next generation? Second-Generation Antipsychotic Drugs Beyond Drugs Nonmedication Therapies When the results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) were

Spun out: Companies born at Wolfson The Wolfson Institute for Biomedical Research was established to bring together the best of industry and academia, so it isn't surprising that several spinout companies have emerged from its walls in recent years. By Stephen Pincock Related Articles Watching Wolfson Ark Therapeutics (1997) has several products in late-stage clinical development, including a gene-based therapy for glioma with orphan drug sta

Second-Generation Antipsychotic Drugs This table lists the atypical antipsychotics. For a story on the lessons of the CATIE trial, click here. For a table of first-generation drugs, click here. For a table of drugs in the pipeline, click here. Drug Brand name(Manufacturer) Approval date Indications Mechanism Cost per 30-day supply* Contraindications/Adverse reactions Injection availability Other data Clozapine Clozaril (N

How to get students to go into science.

To frame, or not to frame? Re: "The future of public engagement,"1 the first thing scientists need to do is abandon all talk of tentativeness, paradigms, and social construct when talking to the public about science. This model of science is appropriate in certain circles, but I see not a shred of evidence that it has improved public scientific literacy, and [I see] a great deal of evidence that it has been used by charlatans to dismiss scientific findings or push bogus alternativ

SIGNALING SYMPOSIA >> Lewis Cantley describes how he discovered a fundamental kinase in numerous cell signaling pathways (see "From Kinase to Cancer."). For more on signaling, check out symposia on the Architecture of Signaling Systems and the Geography of Signaling at the American Society for Cell Biology's annual meeting in Washington, DC, December 1-5. Register at http://ascb.org/meetings. FILL UP ON BLADDERS >> Alison McCook writes about the quest to c

Heidi Elmendorf's passion for parasitology is matched only by her passion for teaching.

Credit: © Joseph T. & Suzanne L. Collins / Photo Researchers, Inc." /> Credit: © Joseph T. & Suzanne L. Collins / Photo Researchers, Inc. The paper: M.C. Brandley et al., "Partitioned Bayesian analyses, partition choice, and the phylogenetic relationships of scincid lizards," Systematic Biol, 54:373-90, 2005. (Cited in 73 papers) The finding: Tod Reeder's group at San Diego State University and a Swiss colleague suggested a revise

Credit: © Oliver Meckes / Nicole Ottawa / Photo Researchers, Inc." /> Credit: © Oliver Meckes / Nicole Ottawa / Photo Researchers, Inc. The paper: M. Könneke et al., "Isolation of an autotrophic ammonia-oxidizing marine archaeon," Nature, 437:543-6, 2005. (Cited in 85 papers) The finding: David Stahl and colleagues from the University of Washington and Woods Hole Oceanographic Institute were investigating nitrification in the Plum Island Sound e

Credit: MethoxyRoxy / WIKIMEDIA" /> Credit: MethoxyRoxy / WIKIMEDIA The paper: D.C. Lie et al., "Wnt signaling regulates adult hippocampal neurogenesis," Nature, 437:1370-5, 2005. (Cited in 79 papers) The finding: After discovering neurogenesis in humans in 1998, Fred Gage's group at the Salk Institute in California went looking for signals that control the phenomenon in rodents. They found that overexpressing the signaling molecule Wnt increased neurogenesis, w

The enzyme AMP-activated protein kinase (AMPK) has been shown to be central to regulating several metabolic systems such as glucose uptake, oxidation of fatty acids, and insulin sensitivity, but the crystal structure of the mammalian enzyme remained elusive. Bing Xiao and others from the United Kingdom's National Institute for Medical Research used X-ray crystallography to map the structure of AMPK when bound to AMP and ATP, which the enzyme binds competitively,1 illuminating AMPK regul

While looking for regulators of neurogenesis, Hongjun Song at Johns Hopkins University School of Medicine and colleagues found that inhibiting the function of the gene disrupted-in-schizophrenia 1 (DISC1) promoted neurogenic behavior.1 The gene is known as a susceptibility gene for mood disorders and schizophrenia, though this was not the focus of Song et al.'s research. They were interested in a previous observation that DISC1 is highly expressed in two areas of the adult brain that

Credit: © James Cavallini / Photo Researchers, Inc." /> Credit: © James Cavallini / Photo Researchers, Inc. J.C. Hermann et al., "Structure-based activity prediction for an enzyme of unknown function," Nature, 448:775-9, Aug. 16, 2007. The X-ray crystallographic structure of the gene product Tm0936 from the amidohydrolase superfamily, deposited by a structural genomics consortium, was used to dock, score, and sort a library of 22,500 high-energy intermediates

Credit: © 2007 Chris Lake Photography" /> Credit: © 2007 Chris Lake Photography Earlier this year, University of Chicago assistant professor Sean Crosson donned a cowboy hat and rode a giant foam bacterium across a stage as part of a student research presentation. The audience broke into laughter. While exploring the "hidden biology" of undescribed signaling pathways in the bacteria, Caulobacter crescentus, Crosson's group manages to share quite a few laughs, and the la

Related Articles Chasing Rainbows How to Maximize Immunofluorescence Multiplexing Cutting crossover Unsticking Staying bright User: Pok Man Mendy Chan, Mount Sinai School of Medicine, New York The project: Studying expression of G-protein coupled receptors in striatal neurons and their involvement Parkinson's disease. The problem: Metabolically active tissue from postmortem brains in Chan's studies shows high levels of background fluorescence. The s

How to make the most of multicolor immunofluorescence

Related Articles Chasing Rainbows Background glow Cutting crossover Unsticking Staying bright Combine dots and dyes to label the most proteins simultaneously. By doing this, Mario Roederer's group at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., can image 17 colors in its flow cytometry experiments. Stuart Sealfon of Mount Sinai School of Medicine recommends saving quantum dots for the proteins that are the most difficult to pick up, while using org

Related Articles Chasing Rainbows How to Maximize Immunofluorescence Multiplexing Background glow Cutting crossover Staying bright User: Xiaohu Gao, University of Washington, Seattle The project: Characterizing tumor tissue by analyzing as many as five coexpressed proteins in clinical tissue biopsies. The problem: Gao wanted to use quantum dots (Invitrogen) because they allow easier multiplexing, but dots pose two serious aggregation problems. First, each qu

A mesenchymal cell labeled with three dye-conjugated antibodies and a nuclear stain. The top left image is a composite of the four markers. Credit: Courtesy of Matthias Schieker, University of Münich" />A mesenchymal cell labeled with three dye-conjugated antibodies and a nuclear stain. The top left image is a composite of the four markers. Credit: Courtesy of Matthias Schieker, University of Münich User: Matthias Schieker, University of Munich, Germany The p

Related Articles No Longer Lonely at the Top Try it on for size. "You network for a number of reasons--for knowledge, for friends, for business," says CXOnetworking president Mitchell Levy. "When you walk into a networking group you should have a feeling for which [of those] things you want." He suggests trying them on for size. Many groups offer free trials to observe a monthly meeting and get a sense of whether you've found what you're looking for. Smaller is better

Schematic drawing depicting Dr. J.J. Woodward's mechanism for taking photographs through a microscope. Inset: Histological preparations photographed by J.J. Woodward, circa 1876 Credit: Otis Historical Archives, National Museum of Health and Medicine, AFIP, Photo: © Jason Varney | Varneyphoto.com" />Schematic drawing depicting Dr. J.J. Woodward's mechanism for taking photographs through a microscope. Inset: Histological preparations photographed by J.J. Woodward, circa 1876 Credit: Otis His