REPORT: Observing the Average Trajectories of Single
Photons in a Two-Slit Interferometer
Abstract: A consequence of the quantum mechanical uncertainty principle is that one may not discuss the path or "trajectory" that a quantum particle takes, because any measurement
of position irrevocably disturbs the momentum, and vice versa. Using weak measurements, however, it is possible to operationally define a set of trajectories for an ensemble of quantum particles.
We sent single photons emitted by a quantum dot through a double-slit interferometer and reconstructed these trajectories by performing a weak measurement of the photon momentum, postselected
according to the result of a strong measurement of photon position in a series of planes. The results provide an observationally grounded description of the propagation of subensembles of
quantum particles in a two-slit interferometer.
Supporting online material
PERSPECTIVE:
Scaling Up DNA Computation
Abstract: Computation is increasingly pervasive. Silicon-based computing devices are embedded in a wide variety of manufactured goods and appliances, increasing functionality,
communication, and control. An analogous development of molecular-scale computing devices could allow similar advantages at vastly smaller scale. For example, embedding molecular-scale computing
devices in biological materials such as serum, cells, or tissues could be used to detect, and possibly treat, disease. On page 1196 of the 3 June 2011 issue of Science, Qian and
Winfree show how such molecular-scale computing devices might be engineered.
NEWS & ANALYSIS: Quake Experts to Be Tried for
Manslaughter
Summary: Seven scientists and technicians who analyzed seismic activity ahead of the devastating earthquake that struck the Italian town of L'Aquila on 6 April 2009 will
indeed face trial for manslaughter, a judge announced last week. The defendants are members of Italy's great risks committee, whose job is to assess risks of potential natural disasters.
A year ago, they were accused by L'Aquila prosecutors of having failed to provide adequate warning of the magnitude-6.3 earthquake that killed 308 people. Given the uncertainties in earthquake
predictions, the accusation surprised and angered many. Thousands of seismologists signed a letter of protest, and international scientific groups, including AAAS (publisher of Science),
condemned the prosecutor's plan to bring manslaughter charges. Nevertheless, Judge Giuseppe Gargarella ruled last week that the case should go to trial.
NEWS & ANALYSIS:
Scientists Rush to Study Genome of Lethal E. coli
Summary: As Science went to press, scientists have not been able to find the source of the deadliest outbreak of enterohemorrhagic Escherichia coli (EHEC)
bacteria on record. Yet they are getting to know the pathogen causing it in unprecedented detail, aided by an armada of scientists around the world who are analyzing available genomic data
on the fly and, via tweets, wikis, and blogs, disseminating results online.
REPORT: Nicotine Decreases Food Intake Through
Activation of POMC Neurons
Abstract: Smoking decreases appetite, and smokers often report that they smoke to control their weight. Understanding the neurobiological mechanisms underlying the anorexic
effects of smoking would facilitate the development of novel treatments to help with smoking cessation and to prevent or treat obesity. By using a combination of pharmacological, molecular
genetic, electrophysiological, and feeding studies, we found that activation of hypothalamic a3ß4 nicotinic acetylcholine receptors leads to activation of pro-opiomelanocortin
(POMC) neurons. POMC neurons and subsequent activation of melanocortin 4 receptors were critical for nicotinic-induced decreases in food intake in mice. This study demonstrates that nicotine
decreases food intake and body weight by influencing the hypothalamic melanocortin system and identifies critical molecular and synaptic mechanisms involved in nicotine-induced decreases
in appetite.
Supporting online material
PERSPECTIVE:
Why Finance Matters
Summary: Roughly one-half of the world's adults, about 2.5 billion people, have neither a bank account nor access to semiformal financial services such as "microcredit," the
growing practice in developing nations of providing small loans, typically less than US$500, to self-employed people. But what if they did? Muhammad Yunus, the 2006 Nobel Peace Prize winner
and founder of Bangladesh's Grameen Bank, a pioneering microcredit institution, argues that this lack of financial access means that the poor, especially poor women, can't obtain the loans
they need to build their businesses and get on a path out of poverty. The idea has taken hold: In 2009, for instance, Grameen Bank served 8 million customers; its average loan balance was
just $127. Worldwide, microcredit advocates now claim more than 190 million customers. Proof of concept, however, is not proof of impact. Recent studies have found that some efforts to provide
small loans have produced surprisingly weak results, and on page 1278 of the 10 June 2011 issue of Science, Karlan and Zinman provide more evidence that we need to rethink microcredit.
Their findings, from a randomized evaluation of microcredit lending in the Philippines, add to a handful of recent results that suggest that microcredit's effectiveness has been overstated
by studies that selectively focus on success stories.
NEWS & ANALYSIS: Citizens Find Radiation Far
From Fukushima
Summary: Frustrated by a dearth of information on what happened to all of the radiological isotopes released from the ravaged Fukushima nuclear power plant, civic groups
and individuals have been monitoring radiation on their own. Collectively, they have produced a worrisome picture of contamination throughout eastern Japan, with some hot spots surprisingly
far from the crippled reactors.
RESEARCH
ARTICLE: EPOXI at Comet Hartley 2
Abstract: Understanding how comets work--what drives their activity--is crucial to the use of comets in studying the early solar system. EPOXI (Extrasolar Planet Observation
and Deep Impact Extended Investigation) flew past comet 103P/Hartley 2, one with an unusually small but very active nucleus, taking both images and spectra. Unlike large, relatively inactive
nuclei, this nucleus is outgassing primarily because of CO2, which drags chunks of ice out of the nucleus. It also shows substantial differences in the relative abundance of volatiles
from various parts of the nucleus.
Supporting online material
NEWS FOCUS: Green Genomes
Summary: Nearly 30 plant genomes are now available for analysis and comparison, containing no shortage of surprises and insights into how the planet's flora and their DNA
evolve. To date, angiosperms, flowering plants that produce seeds and make up the majority of flora seen on Earth today, dominate the roster of the sequenced genomes. But a few other genomes
come from species--algae, a moss, the spikemoss--representing key stages in the evolution of land plants. These DNA sequences are beginning to reveal what it took for plants to move onto
land, grow tall, and produce seeds and flowers. For example, many genes key to the colorful blossoms that brighten the landscape turn out to have unexpectedly deep evolutionary roots, some
stretching back to algae. The genomes are also showing that plant evolution is surprisingly dynamic.
Podcast Interview
PERSPECTIVE: Why Did You Lévy?
Summary: Nature is full of biological landscapes that seem static to the casual observer, but actually contain highly dynamic spatial features. These features are shaped
dramatically, if slowly, by subtle interplays between large-scale population-level patterns and small-scale movements of individual organisms. For spatial ecologists, a challenging aspect
of such landscapes is the chicken-and-egg character of the underlying interactions: Organism movements are dictated by the environment, but the environment is strongly affected by organism
movements. On page 1551 of the 24 June 2011 issue of Science, de Jager et al. reveal how, for mussels in patchy intertidal beds, the ecology of dynamic spatial patterns
and the evolution of movement strategies are tightly linked.
EDITORIAL:
Education Is Not a Race
Summary: In the United States and elsewhere, the competitive pressures placed on young people in school are damaging many otherwise promising lives. In addition to generating
debilitating anxiety and encouraging a culture of cheating, this competition takes the joy out of learning. The film Race to Nowhere, which continues to receive attention since its
release a year ago, documents the unhealthy consequences of the competitive teach to the test climate that many U.S. students experience. The film, in which I was interviewed, puts in clear
relief the pressures that youth are under to amass large numbers of Advanced Placement (college-equivalent) classes, win science fairs, excel in the arts and sports, and in other ways distinguish
themselves from the competition for admission into a few select universities that parents and schools believe are critical for future success. Research on motivation makes it clear that focusing
attention entirely on performance, whether grades or test scores, destroys whatever intrinsic interest the subject matter might have had. There are certainly students whose passions spur
them to realize their full potential in rigorous academic courses and other impressive activities. But how many potential Nobel Prize winners have written off science before the end of high
school because their only exposure to the subject had been in test preparation courses rather than in classes that delved into meaningful questions? It doesn't have to be this way, but change
will require coordinated efforts at many levels.
NEWS FOCUS: Getting There
Summary: Last month, researchers reported creating a new battery design called a semisolid flow cell that's like a battery with a fuel tank. Like today's batteries, the device
contains lithium ions that shuttle back and forth either storing or releasing electrical charges on demand. But instead of packaging those ions along with the electrodes and other apparatus
all together, as in a typical battery, the semisolid flow cell separates the energy-delivery apparatus from energy storage. The new setup can store up to 30 times as much energy as previous
versions. The flow cell still faces a host of challenges, such as ensuring that lithium-containing particles don't settle to the bottom of the battery tank. But if the boldest projects now
in labs around the globe succeed, they could provide at least 10 times the energy of today's lithium-ion batteries, enough to make fully battery-powered cars competitive with today's gasoline
models.
Podcast Interview
In Science Signaling
RESEARCH ARTICLE: TWIK-1 Two-Pore Domain Potassium Channels
Change Ion Selectivity and Conduct Inward Leak Sodium Currents in Hypokalemia
Editor's Summary: When the serum potassium drops to very low concentrations (pathological hypokalemia), the resting membrane potential of human cardiomyocytes can depolarize,
rather than hyperpolarizing as would be predicted by the Nernst equation. This paradoxical depolarization, which is thought to be mediated by an inward sodium current, may contribute to the
abnormalities of cardiac rhythm that can occur under conditions of pathological hypokalemia--or even cardiac arrest. Here, Ma et al. show that the ion selectivity of TWIK-1 channels,
members of a class of potassium-selective ion channels that help maintain the resting membrane potential, changes at subphysiological extracellular potassium concentrations, so that they
become permeable to sodium as well. Ectopic expression of TWIK-1 channels in a mouse cardiomyocyte cell line led to paradoxical depolarization in the presence of low extracellular potassium,
whereas loss of TWIK-1 in cultured human cardiomyocytes abolished their paradoxical depolarization. Thus, by losing their selectivity for potassium and becoming permeable to sodium, TWIK-1
channels may contribute to cardiac paradoxical depolarization in pathological hypokalemia.
Supplementary material
RESEARCH ARTICLE: TRPS1 Targeting by miR-221/222 Promotes
the Epithelial-to-Mesenchymal Transition in Breast Cancer
Editor's Summary: MicroRNAs (miRNAs), short noncoding RNAs that bind to and silence target mRNAs, have emerged as playing crucial regulatory roles not only in normal cellular
processes but also in pathological conditions, such as cancer. Stinson et al. analyzed miRNA expression in different types of human breast cancer and found that miR-221 and miR-222
(miR-221/222) abundance was increased in the clinically aggressive basal-like subtype compared to the less aggressive luminal subtype. They determined that signaling through the epidermal
growth factor receptor (EGFR)-RAS-extracellular signal-regulated kinase (ERK) pathway increased miR-221/222 transcription, and they defined a transcriptional regulatory pathway through which
miR-221/222 promoted a phenotype associated with cancer cell invasion and metastasis. Their data suggest that combining inhibition of the EGFR-RAS-ERK pathway with standard chemotherapy could,
by limiting miR-221/222 production, provide a strategy to combat metastasis in the basal-like subtype of breast cancer.
Supplementary material
PRESENTATIONS: HIF-1a Mediates Tumor Hypoxia to
Confer a Perpetual Mesenchymal Phenotype for Malignant Progression
Abstract: Although tumor progression involves genetic and epigenetic alterations to normal cellular biology, the underlying mechanisms of these changes remain obscure. Numerous
studies have shown that hypoxia-inducible factor 1a (HIF-1a) is overexpressed in many human cancers and up-regulates a host of hypoxia-responsive genes for cancer growth and survival.
We recently identified an alternative mechanism of HIF-1a function that induces genetic alterations by suppressing DNA repair. Here, we show that long-term hypoxia, which mimics the
tumor microenvironment, drives a perpetual epithelial-mesenchymal transition (EMT) through up-regulation of the zinc finger E-box binding homeobox protein ZEB2, whereas short-term hypoxia
induces a reversible EMT that requires the transcription factor Twist1. Moreover, we show that the perpetual EMT driven by chronic hypoxia depends on HIF-1a induction of genetic alterations
rather than its canonical transcriptional activator function. These mesenchymal tumor cells not only acquire tumorigenicity but also display characteristics of advanced cancers, including
necrosis, aggressive invasion, and metastasis. Hence, these results reveal a mechanism by which HIF-1a promotes a perpetual mesenchymal phenotype, thereby advancing tumor progression.
slide show
In Science Translational Medicine
RESEARCH ARTICLE: MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated
Immune Response to Pandemic Influenza Vaccines
Abstract: Oil-in-water adjuvants have been shown to improve immune responses against pandemic influenza vaccines as well as reduce the effective vaccine dose, increasing
the number of doses available to meet global vaccine demand. Here, we use genome fragment phage display libraries and surface plasmon resonance to elucidate the effects of MF59 on the quantity,
diversity, specificity, and affinity maturation of human antibody responses to the swine-origin H1N1 vaccine in different age groups. In adults and children, MF59 selectively enhanced antibody
responses to the hemagglutinin 1 (HA1) globular head relative to the more conserved HA2 domain in terms of increased antibody titers as well as a more diverse antibody epitope repertoire.
Antibody affinity, as inferred by greatly diminished (=10-fold) off-rate constants, was significantly increased in toddlers and children who received the MF59-adjuvanted vaccine. Moreover,
MF59 also improved antibody affinity maturation after each sequential vaccination against avian H5N1 in adults. For both pandemic influenza vaccines, there was a close correlation between
serum antibody affinity and virus-neutralizing capacity. Thus, MF59 quantitatively and qualitatively enhances functional antibody responses to HA-based vaccines by improving both epitope
breadth and binding affinity, demonstrating the added value of such adjuvants for influenza vaccines.
Supplementary material
RESEARCH ARTICLE: Protein Interactome Reveals Converging Molecular Pathways
Among Autism Disorders
Abstract: To uncover shared pathogenic mechanisms among the highly heterogeneous autism spectrum disorders (ASDs), we developed a protein interaction network that identified
hundreds of new interactions among proteins encoded by ASD-associated genes. We discovered unexpectedly high connectivity between SHANK and TSC1, previously implicated in syndromic autism,
suggesting that common molecular pathways underlie autistic phenotypes in distinct syndromes. ASD patients were more likely to harbor copy number variations that encompass network genes than
were control subjects. We also identified, in patients with idiopathic ASD, three de novo lesions (deletions in 16q23.3 and 15q22 and one duplication in Xq28) that involve three network genes
(NECAB2, PKM2, and FLNA). The protein interaction network thus provides a framework for identifying causes of idiopathic autism and for understanding molecular
pathways that underpin both syndromic and idiopathic ASDs.
Supplementary material
REPORT: Whole-Genome Sequencing for Optimized Patient Management
Abstract: Whole-genome sequencing of patient DNA can facilitate diagnosis of a disease, but its potential for guiding treatment has been under-realized. We interrogated the
complete genome sequences of a 14-year-old fraternal twin pair diagnosed with dopa (3,4-dihydroxyphenylalanine)-responsive dystonia (DRD; Mendelian Inheritance in Man #128230). DRD is a genetically
heterogeneous and clinically complex movement disorder that is usually treated with l-dopa, a precursor of the neurotransmitter dopamine. Whole-genome sequencing identified compound heterozygous
mutations in the SPR gene encoding sepiapterin reductase. Disruption of SPR causes a decrease in tetrahydrobiopterin, a cofactor required for the hydroxylase enzymes that
synthesize the neurotransmitters dopamine and serotonin. Supplementation of l-dopa therapy with 5-hydroxytryptophan, a serotonin precursor, resulted in clinical improvements in both twins.
Supplementary material
RESEARCH ARTICLE: Dosage Thresholds for AAV2 and AAV8 Photoreceptor Gene
Therapy in Monkey
Abstract: Gene therapy is emerging as a therapeutic modality for treating disorders of the retina. Photoreceptor cells are the primary cell type affected in many inherited
diseases of retinal degeneration. Successfully treating these diseases with gene therapy requires the identification of efficient and safe targeting vectors that can transduce photoreceptor
cells. One serotype of adeno-associated virus, AAV2, has been used successfully in clinical trials to treat a form of congenital blindness that requires transduction of the supporting cells
of the retina in the retinal pigment epithelium (RPE). Here, we determined the dose required to achieve targeting of AAV2 and AAV8 vectors to photoreceptors in nonhuman primates. Transgene
expression in animals injected subretinally with various doses of AAV2 or AAV8 vectors carrying a green fluorescent protein transgene was correlated with surgical, clinical, and immunological
observations. Both AAV2 and AAV8 demonstrated efficient transduction of RPE, but AAV8 was markedly better at targeting photoreceptor cells. These preclinical results provide guidance for
optimal vector and dose selection in future human gene therapy trials to treat retinal diseases caused by loss of photoreceptors.
Supplementary material
IMAGE CREDITS (In order of appearance): Y. HAMMOND/SCIENCE, CHRISTIAN CHARISIUS/AFP/GETTY IMAGES/NEWSCOM, ROBIN SAIDMAN/VITALEDGE, CORBIS
