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New Choice for Science

Geophysicist Marcia McNutt will be taking over the editor-in-chief slot at Science, reports the Nature News Blog. Previously, McNutt was the director of the US Geological Survey and, before that, she was the president and CEO of the Monterey Bay Aquarium Research Institute in California. In addition, McNutt served on Science's senior editorial board between 2000 and 2009, giving her a taste of what running the journal may be like. "It gave me a chance to know many of the editors and staff at Science, and to understand at a high level a lot of the decisions that the editor-in-chief is responsible for," she tells ScienceInsider.

She also tells the Nature News Blog that she is coming to the post without too many plans. "I think it's dangerous … to come in with too much of a set agenda, because that can mean that you are speaking too much, and not listening enough," she adds.

McNutt, who will be starting at Science at the beginning of June, is succeeding Bruce Alberts, who announced last May that he was stepping down from the editor-in-chief position.

April 03, 2013

This Week in Nucleic Acids Research

In the advance access edition of Nucleic Acids Research, National Institutes of Health researchers summarize findings from genomic studies on archaea and bacteria, focusing in particular on defense strategies uncovered in the prokaryotic microbes via comparative genomics. Such data have helped in delineating the types of defense systems that are sprinkled across the archaeal and bacterial phylogenies, the team says, highlighting the propensity for defense genes to cluster, for instance, and revealing ties between genes contributing to immune system function and those in place to prompt dormancy or cell suicide.

A Japanese team presents a new statistical method for calling somatic mutations in cancer genomes using high-throughput sequence data. The strategy — known as empirical Bayesian mutation calling, or EBCall — relies on a Bayesian statistical model to help find situations in which allele frequencies don't match patterns predicted from known sequencing error profiles, the researchers say. In addition to describing the rationale behind their approach, authors of the study demonstrate the utility of EBCall, using whole-exome sequence data on paired tumor-normal samples to call mutations stretching into the low frequency range in coding regions of the tumors.

A study by researchers from Wayne State University and elsewhere highlights the variety of RNA molecules found in sperm cells and that apparently contribute to the function of these reproductive cells. The group used RNA sequencing to follow shifts in coding and non-coding RNA representatives present in human sperm during development, looking also at factors influencing this collection. The population of RNA in sperm as revealed by RNA-seq provides a window into the developmental history, functional viability, and potential elements present by sperm that may serve a role in the final stages of spermiogenesis or at fertilization," the study authors say.

April 03, 2013

Just Part of the Salad

Researchers from the University of Colorado, Boulder, examined the microbes found on fresh fruits and vegetables at area grocery stores using 16S ribosomal gene sequencing. As they report in PLOS One, the different types of produce — they sampled apples, grapes, spinach, alfalfa, and more — harbored different microbes. "Mung bean sprouts, for one, harbor very different bacteria than alfalfa sprouts," Nancy Shute at NPR's The Salt notes. "Grapes, apples and peaches house a greater variety of bacteria than veggies." Other produce, though, like strawberries, tomatoes and spinach, she says, appear to contain more similar surface bacteria.

Further, the Boulder scientists found that there were differences between conventional and organic samples of the same types of produce, as the organic varieties typically had more diverse microbes. "We can't say that this is attributable to the farming practice itself," lead author Jonathan Leff tells The Salt. "It could be transport and storage." He adds that how the diversity of microbes on fruits and veggies influences human health is also unknown.

April 02, 2013

Dysfunction and the Medical Revolution

The federal sequestration is cutting back or halting grants that fund "potentially groundbreaking" personalized medicine research funded by the National Institutes of Health, Institute for Systems Biology President Lee Hood opines.

Taking his pen to the pages of The Hill, Hood writes that political three-way fisticuffs between lawmakers in both houses and the White House that led to the sequester — an across-the-board five percent whack to all agency budgets — could imperil advances in personalized medicine research that ISB is pursuing.

Hood praises the promise of what he calls P4 medicine, the convergence of new big data and genomic technologies to develop "medicine that is predictive, personalized, preventive, and participatory."

The forward march of P4 will bring about a new type of medicine, Hood writes, that will improve care through diagnoses and targeted therapies. It also will save money in the long run because new and better treatments and predictive medicine will "reduce the skyrocketing costs of healthcare" and help create new "wellness sector" markets and companies that don't yet exist, he says.

"In 1986, the automated DNA sequencer I invented was first brought to market, paving the way for the Human Genome Project completed in 2003. In 2010 alone, human genome sequencing activities generated $67 billion in US economic output and created 310,000 US jobs," he says.

Hood doesn't want to see a dysfunctional political culture on Capitol Hill hinder the advance of these technologies, markets, and medical innovations.

"On the 10th anniversary of the completion of the Human Genome Project, we can't let the ongoing tug-of-war in Congress over spending priorities threaten the revolutionary work that is taking place in medical science," he writes.

April 02, 2013 / 2 comments

A Way Around

Messenger RNAs are once again capturing the attention of pharmaceutical companies as a class of drugs, writes Susan Young at MIT's Technology Review. In the past, mRNAs had garnered interest, but then had been abandoned as they can also set off an immune response.

But new ways to work around their unwanted effects have been found, Young says. For example, she notes that Moderna — which has recently entered a $240 million agreement with AstraZeneca for it to use Moderna technology to develop therapeutics — uses some mRNA nucleotide analogs to avoid the immune system labeling it as harmful. That change also strengthens, she says, the known fragility of mRNAs so that they can last longer in patients and be taken up by their cells.

"The beauty is that the patient's cells produce the drug," Carsten Rudolph, CEO of Ethris, tells Young. Because patients produce the drug, he adds, there is less of a chance of an adverse immune reaction. Ethris, meanwhile, has joined with Shire to develop treatments based on its own technology.

April 02, 2013

BRAIN Game

US President Barack Obama is to announce his $100 million initiative to map the human brain today, the New York Times reports. A senior administration scientist likens the initiative, called the Brain Research Through Advancing Innovative Neurotechnologies or BRAIN, to the Human Genome Project.

The AP notes that Obama mentioned the project in his State of the Union address to Congress in February. "Every dollar we invested to map the human genome returned $140 to our economy. Every dollar," Obama said then. "Today, our scientists are mapping the human brain to unlock the answers to Alzheimer's."

The project, the Times adds, will involve a number of agencies, including the National Institutes of Health, National Science Foundation, and the Defense Advanced Research Projects Agency. A so-called "dream team" of researchers led by Rockefeller University's Cori Bargmann and William Newsome from Stanford University will be developing a specific plan and goals for the project.

April 02, 2013 / 2 comments

This Week in PNAS

In the early, online edition of the Proceedings of the National Academy of Sciences, an international team describes unexpected findings from a mitochondrial DNA analysis of ancient Botocudo Indian skull samples from Brazil. When they assessed mtDNA sequences from 14 Botocudo samples — believed to stretch back to the 19th century —investigators determined that a dozen of the individuals belonged to a mitochondrial haplogroup associated with Amerindian populations. But two of the ancient individuals carried mitochondrial sequences most closely matching a Polynesian haplogroup. "We have entertained several possible models to try to explain how these Polynesian sequences were found in individuals from an Amerindian population living in a region in the interior of Brazil," they study's authors noted, adding that, "our results do not allow us to accept or definitely reject any of these scenarios."

Maize genotype at least partly influences the microbial communities found in the rhizosphere region around plant roots, according to a study by Cornell University's Ruth Ley and colleagues from Cornell, the Department of Energy's Joint Genome Institute, and University of North Carolina at Chapel Hill. The team used 16S ribosomal sequencing to assess rhizosphere microbiomes in plants from 27 inbred maize lines grown under five field conditions in three states. "The rhizospheres from maize inbreds exhibited both a small but significant proportion of heritable variation in total bacterial diversity across fields," the researchers note, "and substantially more heritable variation between replicates of the inbreds within each field."

University of California, Berkeley, researchers offer an account of sex-biased gene expression in the emu in another online PNAS paper. Using a combination of genome and transcriptome sequence data, the group verified the gene content similarities between the bird's Z and W sex chromosomes. But findings from the study also indicated that sex-linked genes on these chromosomes are prone to rampant sex-biased expression in the emu, offering new information about the basis of sex chromosome evolution in emus and related ratite birds. "Additional genomic analysis of the sex chromosomes of other birds, and in particular other ratites, should allow us to further refine the evolutionary history of the avian sex chromosomes," Berkeley's Doris Bachtrog and colleagues conclude.

April 02, 2013

Survey Morale

A survey of MD Anderson Cancer Center faculty shows dissatisfaction with its leadership, the Nature News blog reports. Nearly 74 percent of the respondents to the survey, obtained by The Cancer Letter, say that faculty morale is worse than when a previous faculty survey was conducted in 2010. Among the reasons given by respondents as to why morale has declined include a lack of transparency and conflict of interest concerns regarding the institute's president, Ronald DePinho.

DePinho and his wife Lynda Chin, who is a researcher at MD Anderson, have been embroiled in controversy regarding an incubator grant awarded to Chin by the Cancer Prevention and Research Institute of Texas without undergoing scientific review. (CPRIT said in May that it would be giving the grant another look.) Additionally, the Nature News blog says DePinho had to apologize in June for promoting the stock of a company that he co-founded on TV without disclosure of that relationship.

The Cancer Letter notes that only about a third of MD Anderson faculty members responded to the survey, and that those who were angrier might have been more likely to respond than people who were happy.

"Some of the feedback was humbling and constructive, and I've taken to heart the survey's results, as well as what faculty have told me directly about what we can do to move the institution forward," DePinho tells The Cancer Letter.

April 01, 2013

The Costs

Nature, in its current issue, takes a look at the state of scientific publishing. In one article, Richard Van Noorden examines the costs of scientific publishing, both publishing fees and publishers' profits.

With the rise of open-access journals, "suddenly, scientists can compare between different publishing prices," he writes. "A paper that costs US$5,000 for an author to publish in Cell Reports, for example, might cost just $1,350 to publish in PLOS One — whereas PeerJ offers to publish an unlimited number of papers per author for a one-time fee of $299."

Journals, he notes, have different profit margins that may contribute to those costs. Citing data from Outsell, a consulting firm, Van Noorden says that the average cost of publishing a scientific paper likely ranges between $3,500 and $4,000, and the average revenue for the publisher per article is about $5,000. Numbers for specific journals, he adds, are harder to come by, but he writes that Wiley used to say that it had a 40 percent profit margin before taxes on its science publishing division, while Elsevier has reported a 37 percent margin, though Van Noorden adds that some analysts say that percentage may be higher. Open-access publishers, too, make money; he reports that Hindawi made a 50 percent profit last year.

"But the difference in profit margins explains only a small part of the variance in per-paper prices. One reason that open-access publishers have lower costs is simply that they are newer, and publish entirely online, so they don't have to do print runs or set up subscription paywalls. … Still, most older publishers are investing heavily in technology, and should catch up eventually," he adds.

HT: Derek Lowe at In the Pipeline

April 01, 2013 / 1 comment

This Week in PLOS

University of Colorado at Boulder researchers Jonathan Leff and Noah Feirer took stock of the microbial communities found on fresh fruits and vegetables for a PLOS One study. The pair used 16S ribosomal gene sequencing to canvass microbial community members on 11 types of fruit and vegetables purchased at Boulder grocery stores (including organic and non-organic representatives, in most cases). Some fruit and vegetable microbiomes showed similarities when researchers considered the most prevalent bacterial families. Even so, investigators saw that each type of produce carried distinguishable microbiomes, as did the organic and conventionally farmed versions of these fruits and vegetables.

In PLOS Genetics, members of the Collaborative Oncological Gene-environment Study, or COGS, initiative describe their search for ovarian and/or breast cancer risk modifiers in individuals carrying alterations in the BRCA1 and/or BRCA2 genes.

In the first of these, COGS members considered almost 12,000 individuals with BRCA1 mutations, including 5,920 individuals with breast cancer and 1,839 individuals with ovarian cancer. Through a multi-stage genome-wide association study involving these and other women, they narrowed in on a chromosome 1 locus that appears to mediate breast cancer risk in those with BRCA1 mutations as well risk loci on chromosomes 4 and 17 that modify ovarian cancer risk in those with risky BRCA1 gene glitches. A similar GWAS involving thousands of individuals carrying BRCA2 mutations — 3,881 with and 4,330 without breast cancer — turned up a new breast cancer risk modifier on chromosome 6.

Meanwhile, a third COGS paper, also in PLOS Genetics, looks at the interplay between genetic contributors to breast cancer and environmental risk factors for the disease. Findings from that analysis "provide [the] first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors," its authors conclude.

All three cancer studies were part of a 13-paper collection published by COGS researchers last week.

April 01, 2013

The Weight of the Microbiome

The microbes lurking in the human or mouse gut may influence the weight of that person or mouse. The New York Times points out two new studies that "reflect a growing awareness of the crucial role played by the trillions of bacteria and other microorganisms that live in their own ecosystem in the gut."

In one study, published in Science Translational Medicine, Massachusetts General Hospital's Lee Kaplan and colleagues examine how gastric bypass surgery affects the gut microbiome of a mouse model of obesity. Mice that underwent surgery exhibited changes to their microbiomes, with different levels of Gammaproteobacteria and Verrucomicrobia, while those that underwent a sham operation or sham surgery plus calorie restriction did not. Further, when these post-surgery microbiomes were transferred into other mice, those mice lost weight.

In a separate paper in the Journal of Clinical Endocrinology and Metabolism, a team led by Ruchi Mathur at Cedars-Sinai Medical Center found that people with higher BMIs and body fat also had higher methane and hydrogen levels, as detected by a breath test. The researchers attributed those levels to increased numbers of Methanobrevibacter smithii, which require hydrogen, in their guts. "The people with the highest readings on the breath test were more likely to be heavier and have more body fat, and the researchers suspect that the microbes may be at least partly responsible for their obesity," the Times says.

March 29, 2013

Debating the Incidental

On The Takeaway this week, host Todd Zwillich bridged two brief arguments on somewhat opposing sides of the debate over the new American College of Medical Genetics and Genomics recommendations on disclosing incidental findings from genome sequencing.

In a segment on Monday, Arthur Caplan head of the Division of Medical Ethics at the NYU Langone Medical Center told Zwillich that the new report — recommending that all labs performing genome sequencing should notify physicians about their patients' status for a set of 24 conditions, genes, and variants and that doctors who receive this information must share it with their patients — could potentially scare patients away from genomic testing.

Caplan worries especially about the provision that doctors should tell patients, whether they want to know or not, about their genetic risk status for these 24 conditions.

"When you take a test, someone has to ask you if you want to know the results, particularly if those results are not what you came for," he said.

In a rebuttal Tuesday, Robert Green, a medical geneticist at Brigham and Women's Hospital and an author of the new recommendations said the working group spent 14 months "agonizing over" questions on what information should be reported to physicians and what should not, coming up with an "extremely short list of genes and conditions," that allow for the possibility of treatment or amelioration in some way.

Green argued that genetic information is just another tool for identifying and exploring patient's risk of disease, and should be treated the same way as other tools in the medical testing repertoire.

"This is nothing new," he said. An x-ray technician who sees a shadow in a patient's lung is required to put that in a report to the physician, who is ethically bound to investigate it with his patient.

"[The recommendations are] a way for us to bring genomic information in line with the way we treat the rest of medical care information," Green said.

March 29, 2013 / 1 comment

On the List

One of the reasons that papers get retracted is because of authorship issues, write Adam Marcus and Ivan Oransky, who run the Retraction Watch blog, at Lab Times.

"What’s the best way to acknowledge the work of colleagues who might have helped provide intellectual background for a particular study but who did not participate in the collection of the data or the preparation of the manuscript?" they ask. "And what of the lab head, whose ability to bring in money keeps the lights on and the rats fed?"

Marcus and Oransky point out that journals and other organizations provide guidelines to help researchers determine who should and who should not be included on the author list. Elsevier, they note, says that authors must "have made a significant contribution to the conception, design, execution, or interpretation of the reported study."

But getting at that question of the lab head, Marcus and Oransky add that the Committee on Publication Ethics says that such senior figures, if they did not make that substantial contribution to the work, should not be listed as authors.

March 29, 2013 / 1 comment