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Showing papers by "Massachusetts Institute of Technology published in 2010"


Journal ArticleDOI
15 Apr 2010-Nature
TL;DR: It is shown that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression, indicating that l incRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.
Abstract: Large intervening non-coding RNAs (lincRNAs) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodelling activities. Here we show that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression. The lincRNA termed HOTAIR is increased in expression in primary breast tumours and metastases, and HOTAIR expression level in primary tumours is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb repressive complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.

4,605 citations


Journal ArticleDOI
19 Feb 2010-Science
TL;DR: The Kepler mission was designed to determine the frequency of Earth-sized planets in and near the habitable zone of Sun-like stars, which is the region where planetary temperatures are suitable for water to exist on a planet's surface.
Abstract: The Kepler mission was designed to determine the frequency of Earth-sized planets in and near the habitable zone of Sun-like stars. The habitable zone is the region where planetary temperatures are suitable for water to exist on a planet’s surface. During the first 6 weeks of observations, Kepler monitored 156,000 stars, and five new exoplanets with sizes between 0.37 and 1.6 Jupiter radii and orbital periods from 3.2 to 4.9 days were discovered. The density of the Neptune-sized Kepler-4b is similar to that of Neptune and GJ 436b, even though the irradiation level is 800,000 times higher. Kepler-7b is one of the lowest-density planets (~0.17 gram per cubic centimeter) yet detected. Kepler-5b, -6b, and -8b confirm the existence of planets with densities lower than those predicted for gas giant planets.

3,663 citations


Journal ArticleDOI
TL;DR: The epigenetic landscape of enhancer elements in embryonic stem cells and several adult tissues in the mouse is interrogated and it is found that histone H3K27ac distinguishes active enhancers from inactive/poised enhancers and poised enhancer networks provide clues to unrealized developmental programs.
Abstract: Developmental programs are controlled by transcription factors and chromatin regulators, which maintain specific gene expression programs through epigenetic modification of the genome. These regulatory events at enhancers contribute to the specific gene expression programs that determine cell state and the potential for differentiation into new cell types. Although enhancer elements are known to be associated with certain histone modifications and transcription factors, the relationship of these modifications to gene expression and developmental state has not been clearly defined. Here we interrogate the epigenetic landscape of enhancer elements in embryonic stem cells and several adult tissues in the mouse. We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone. This indicates that the amount of actively used enhancers is lower than previously anticipated. Furthermore, poised enhancer networks provide clues to unrealized developmental programs. Finally, we show that enhancers are reset during nuclear reprogramming.

3,541 citations


01 Jun 2010
TL;DR: Results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.
Abstract: MicroRNAs (miRNAs) are endogenous approximately 22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (>/=84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.

3,444 citations


Journal ArticleDOI
12 Aug 2010-Nature
TL;DR: In this paper, the authors used ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels, showing that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.
Abstract: MicroRNAs (miRNAs) are endogenous approximately 22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (>/=84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.

3,401 citations


Journal ArticleDOI
Rameen Beroukhim, Craig H. Mermel1, Craig H. Mermel2, Dale Porter3, Guo Wei1, Soumya Raychaudhuri1, Soumya Raychaudhuri4, Jerry Donovan3, Jordi Barretina1, Jordi Barretina2, Jesse S. Boehm1, Jennifer Dobson1, Jennifer Dobson2, Mitsuyoshi Urashima5, Kevin T. Mc Henry3, Reid M. Pinchback1, Azra H. Ligon4, Yoon Jae Cho6, Leila Haery2, Leila Haery1, Heidi Greulich, Michael R. Reich1, Wendy Winckler1, Michael S. Lawrence1, Barbara A. Weir2, Barbara A. Weir1, Kumiko E. Tanaka1, Kumiko E. Tanaka2, Derek Y. Chiang1, Derek Y. Chiang7, Derek Y. Chiang2, Adam J. Bass4, Adam J. Bass2, Adam J. Bass1, Alice Loo3, Carter Hoffman2, Carter Hoffman1, John R. Prensner2, John R. Prensner1, Ted Liefeld1, Qing Gao1, Derek Yecies2, Sabina Signoretti2, Sabina Signoretti4, Elizabeth A. Maher8, Frederic J. Kaye, Hidefumi Sasaki9, Joel E. Tepper7, Jonathan A. Fletcher4, Josep Tabernero10, José Baselga10, Ming-Sound Tsao11, Francesca Demichelis12, Mark A. Rubin12, Pasi A. Jänne2, Pasi A. Jänne4, Mark J. Daly1, Mark J. Daly2, Carmelo Nucera13, Ross L. Levine14, Benjamin L. Ebert2, Benjamin L. Ebert1, Benjamin L. Ebert4, Stacey Gabriel1, Anil K. Rustgi15, Cristina R. Antonescu14, Marc Ladanyi14, Anthony Letai2, Levi A. Garraway1, Levi A. Garraway2, Massimo Loda4, Massimo Loda2, David G. Beer16, Lawrence D. True17, Aikou Okamoto5, Scott L. Pomeroy6, Samuel Singer14, Todd R. Golub1, Todd R. Golub2, Todd R. Golub18, Eric S. Lander2, Eric S. Lander1, Eric S. Lander19, Gad Getz1, William R. Sellers3, Matthew Meyerson2, Matthew Meyerson1 
18 Feb 2010-Nature
TL;DR: It is demonstrated that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival, and a large majority of SCNAs identified in individual cancer types are present in several cancer types.
Abstract: A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.

3,375 citations


Proceedings ArticleDOI
13 Jun 2010
TL;DR: This paper proposes the extensive Scene UNderstanding (SUN) database that contains 899 categories and 130,519 images and uses 397 well-sampled categories to evaluate numerous state-of-the-art algorithms for scene recognition and establish new bounds of performance.
Abstract: Scene categorization is a fundamental problem in computer vision However, scene understanding research has been constrained by the limited scope of currently-used databases which do not capture the full variety of scene categories Whereas standard databases for object categorization contain hundreds of different classes of objects, the largest available dataset of scene categories contains only 15 classes In this paper we propose the extensive Scene UNderstanding (SUN) database that contains 899 categories and 130,519 images We use 397 well-sampled categories to evaluate numerous state-of-the-art algorithms for scene recognition and establish new bounds of performance We measure human scene classification performance on the SUN database and compare this with computational methods Additionally, we study a finer-grained scene representation to detect scenes embedded inside of larger scenes

2,960 citations


Journal ArticleDOI
TL;DR: Raman spectroscopy is shown to provide a powerful tool to differentiate between two different sp(2) carbon nanostructures (carbon nanotubes and graphene) which have many properties in common and others that differ.
Abstract: Raman spectroscopy is here shown to provide a powerful tool to differentiate between two different sp2 carbon nanostructures (carbon nanotubes and graphene) which have many properties in common and others that differ. Emphasis is given to the richness of both carbon nanostructures as prototype examples of nanostructured materials. A glimpse toward future developments in this field is presented.

2,822 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigated the applicability of synthetic control methods to comparative case studies and found that, following Proposition 99, tobacco consumption fell markedly in California relative to a comparable synthetic control region, and that by the year 2000 annual per-capita cigarette sales in California were about 26 packs lower than what they would have been in the absence of Proposition 99.
Abstract: Building on an idea in Abadie and Gardeazabal (2003), this article investigates the application of synthetic control methods to comparative case studies. We discuss the advantages of these methods and apply them to study the effects of Proposition 99, a large-scale tobacco control program that California implemented in 1988. We demonstrate that, following Proposition 99, tobacco consumption fell markedly in California relative to a comparable synthetic control region. We estimate that by the year 2000 annual per-capita cigarette sales in California were about 26 packs lower than what they would have been in the absence of Proposition 99. Using new inferential methods proposed in this article, we demonstrate the significance of our estimates. Given that many policy interventions and events of interest in social sciences take place at an aggregate level (countries, regions, cities, etc.) and affect a small number of aggregate units, the potential applicability of synthetic control methods to comparative cas...

2,815 citations


Journal ArticleDOI
TL;DR: The 1000 Functional Connectomes Project (Fcon_1000) as discussed by the authors is a large-scale collection of functional connectome data from 1,414 volunteers collected independently at 35 international centers.
Abstract: Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

2,787 citations


Journal ArticleDOI
TL;DR: Genetic loci associated with body mass index map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor, which may provide new insights into human body weight regulation.
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Journal ArticleDOI
TL;DR: The Scope of Review: Large-Scale Centralized Energy Storage, Chemical Energy Storage: Solar Fuels, and Capacitors 6486 5.1.2.
Abstract: 1. Setting the Scope of the Challenge 6474 1.1. The Need for Solar Energy Supply and Storage 6474 1.2. An Imperative for Discovery Research 6477 1.3. Scope of Review 6478 2. Large-Scale Centralized Energy Storage 6478 2.1. Pumped Hydroelectric Energy Storage (PHES) 6479 2.2. Compressed Air Energy Storage (CAES) 6480 3. Smaller Scale Grid and Distributed Energy Storage 6481 3.1. Flywheel Energy Storage (FES) 6481 3.2. Superconducting Magnetic Energy Storage 6482 4. Chemical Energy Storage: Electrochemical 6482 4.1. Batteries 6482 4.1.1. Lead-Acid Batteries 6483 4.1.2. Alkaline Batteries 6484 4.1.3. Lithium-Ion Batteries 6484 4.1.4. High-Temperature Sodium Batteries 6484 4.1.5. Liquid Flow Batteries 6485 4.1.6. Metal-Air Batteries 6485 4.2. Capacitors 6485 5. Chemical Energy Storage: Solar Fuels 6486 5.1. Solar Fuels in Nature 6486 5.2. Artificial Photosynthesis and General Considerations of Water Splitting 6486

Journal ArticleDOI
TL;DR: This paper describes Meep, a popular free implementation of the finite-difference time-domain (FDTD) method for simulating electromagnetism, and focuses on aspects of implementing a full-featured FDTD package that go beyond standard textbook descriptions of the algorithm.

Journal ArticleDOI
06 May 2010
TL;DR: The Soil Moisture Active Passive mission is one of the first Earth observation satellites being developed by NASA in response to the National Research Council's Decadal Survey to make global measurements of the soil moisture present at the Earth's land surface.
Abstract: The Soil Moisture Active Passive (SMAP) mission is one of the first Earth observation satellites being developed by NASA in response to the National Research Council's Decadal Survey SMAP will make global measurements of the soil moisture present at the Earth's land surface and will distinguish frozen from thawed land surfaces Direct observations of soil moisture and freeze/thaw state from space will allow significantly improved estimates of water, energy, and carbon transfers between the land and the atmosphere The accuracy of numerical models of the atmosphere used in weather prediction and climate projections are critically dependent on the correct characterization of these transfers Soil moisture measurements are also directly applicable to flood assessment and drought monitoring SMAP observations can help monitor these natural hazards, resulting in potentially great economic and social benefits SMAP observations of soil moisture and freeze/thaw timing will also reduce a major uncertainty in quantifying the global carbon balance by helping to resolve an apparent missing carbon sink on land over the boreal latitudes The SMAP mission concept will utilize L-band radar and radiometer instruments sharing a rotating 6-m mesh reflector antenna to provide high-resolution and high-accuracy global maps of soil moisture and freeze/thaw state every two to three days In addition, the SMAP project will use these observations with advanced modeling and data assimilation to provide deeper root-zone soil moisture and net ecosystem exchange of carbon SMAP is scheduled for launch in the 2014-2015 time frame

Journal ArticleDOI
TL;DR: An online tool to draw survival plots, which can be used to assess the relevance of the expression levels of various genes on the clinical outcome both in untreated and treated breast cancer patients, and which validated the capability of microarrays to determine estrogen receptor status in 1,231 patients.
Abstract: Validating prognostic or predictive candidate genes in appropriately powered breast cancer cohorts are of utmost interest. Our aim was to develop an online tool to draw survival plots, which can be used to assess the relevance of the expression levels of various genes on the clinical outcome both in untreated and treated breast cancer patients. A background database was established using gene expression data and survival information of 1,809 patients downloaded from GEO (Affymetrix HGU133A and HGU133+2 microarrays). The median relapse free survival is 6.43 years, 968/1,231 patients are estrogen-receptor (ER) positive, and 190/1,369 are lymph-node positive. After quality control and normalization only probes present on both Affymetrix platforms were retained (n = 22,277). In order to analyze the prognostic value of a particular gene, the cohorts are divided into two groups according to the median (or upper/lower quartile) expression of the gene. The two groups can be compared in terms of relapse free survival, overall survival, and distant metastasis free survival. A survival curve is displayed, and the hazard ratio with 95% confidence intervals and logrank P value are calculated and displayed. Additionally, three subgroups of patients can be assessed: systematically untreated patients, endocrine-treated ER positive patients, and patients with a distribution of clinical characteristics representative of those seen in general clinical practice in the US. Web address: www.kmplot.com . We used this integrative data analysis tool to confirm the prognostic power of the proliferation-related genes TOP2A and TOP2B, MKI67, CCND2, CCND3, CCNDE2, as well as CDKN1A, and TK2. We also validated the capability of microarrays to determine estrogen receptor status in 1,231 patients. The tool is highly valuable for the preliminary assessment of biomarkers, especially for research groups with limited bioinformatic resources.

Journal ArticleDOI
TL;DR: In this paper, the characteristics of tropical cyclones have changed or will change in a warming climate and if so, how, has been the subject of considerable investigation, often with conflicting results.
Abstract: Whether the characteristics of tropical cyclones have altered, or will alter, in a changing climate has been subject of considerable debate. An overview of recent research indicates that greenhouse warming will cause stronger storms, on average, but a decrease in the frequency of tropical cyclones. Whether the characteristics of tropical cyclones have changed or will change in a warming climate — and if so, how — has been the subject of considerable investigation, often with conflicting results. Large amplitude fluctuations in the frequency and intensity of tropical cyclones greatly complicate both the detection of long-term trends and their attribution to rising levels of atmospheric greenhouse gases. Trend detection is further impeded by substantial limitations in the availability and quality of global historical records of tropical cyclones. Therefore, it remains uncertain whether past changes in tropical cyclone activity have exceeded the variability expected from natural causes. However, future projections based on theory and high-resolution dynamical models consistently indicate that greenhouse warming will cause the globally averaged intensity of tropical cyclones to shift towards stronger storms, with intensity increases of 2–11% by 2100. Existing modelling studies also consistently project decreases in the globally averaged frequency of tropical cyclones, by 6–34%. Balanced against this, higher resolution modelling studies typically project substantial increases in the frequency of the most intense cyclones, and increases of the order of 20% in the precipitation rate within 100 km of the storm centre. For all cyclone parameters, projected changes for individual basins show large variations between different modelling studies.

Journal ArticleDOI
04 Jan 2010-Small
TL;DR: An understanding of how synthetic and natural chemical moieties on the nanoparticle surface (in addition to nanoparticle shape and size) impact their interaction with lipid bilayers and cells is presented.
Abstract: The interaction of nanomaterials with cells and lipid bilayers is critical in many applications such as phototherapy, imaging, and drug/gene delivery. These applications require a firm control over nanoparticle-cell interactions, which are mainly dictated by surface properties of nanoparticles. This critical Review presents an understanding of how synthetic and natural chemical moieties on the nanoparticle surface (in addition to nanoparticle shape and size) impact their interaction with lipid bilayers and cells. Challenges for undertaking a systematic study to elucidate nanoparticle-cell interactions are also discussed.

Journal ArticleDOI
15 Apr 2010-Nature
TL;DR: Evidence is provided of inducing an RNAi mechanism of action in a human from the delivered siRNA and the presence of an mRNA fragment that demonstrates that siRNA-mediated mRNA cleavage occurs specifically at the site predicted for anRNAi mechanism from a patient who received the highest dose of the nanoparticles.
Abstract: Therapeutics that are designed to engage RNA interference (RNAi) pathways have the potential to provide new, major ways of imparting therapy to patients. Long, double-stranded RNAs were first shown to mediate RNAi in Caenorhabditis elegans, and the potential use of RNAi for human therapy has been demonstrated by the finding that small interfering RNAs (siRNAs; approximately 21-base-pair double-stranded RNA) can elicit RNAi in mammalian cells without producing an interferon response. We are at present conducting the first in-human phase I clinical trial involving the systemic administration of siRNA to patients with solid cancers using a targeted, nanoparticle delivery system. Here we provide evidence of inducing an RNAi mechanism of action in a human from the delivered siRNA. Tumour biopsies from melanoma patients obtained after treatment show the presence of intracellularly localized nanoparticles in amounts that correlate with dose levels of the nanoparticles administered (this is, to our knowledge, a first for systemically delivered nanoparticles of any kind). Furthermore, a reduction was found in both the specific messenger RNA (M2 subunit of ribonucleotide reductase (RRM2)) and the protein (RRM2) levels when compared to pre-dosing tissue. Most notably, we detect the presence of an mRNA fragment that demonstrates that siRNA-mediated mRNA cleavage occurs specifically at the site predicted for an RNAi mechanism from a patient who received the highest dose of the nanoparticles. Together, these data demonstrate that siRNA administered systemically to a human can produce a specific gene inhibition (reduction in mRNA and protein) by an RNAi mechanism of action.

Journal ArticleDOI
22 Jan 2010-Science
TL;DR: A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function.
Abstract: A genome-scale genetic interaction map was constructed by examining 5.4 million gene-gene pairs for synthetic genetic interactions, generating quantitative genetic interaction profiles for ~75% of all genes in the budding yeast, Saccharomyces cerevisiae. A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function. The global network identifies functional cross-connections between all bioprocesses, mapping a cellular wiring diagram of pleiotropy. Genetic interaction degree correlated with a number of different gene attributes, which may be informative about genetic network hubs in other organisms. We also demonstrate that extensive and unbiased mapping of the genetic landscape provides a key for interpretation of chemical-genetic interactions and drug target identification.

Journal ArticleDOI
TL;DR: A precisely defined method for automatically labeling the cortical surface in standard terminology using standard internationally accepted nomenclature and criteria is presented.

Journal ArticleDOI
03 Sep 2010-Science
TL;DR: In this paper, the authors investigated the effects of network structure on diffusion by studying the spread of health behavior through artificially structured online communities and found that individual adoption was much more likely when participants received social reinforcement from multiple neighbors in the social network.
Abstract: How do social networks affect the spread of behavior? A popular hypothesis states that networks with many clustered ties and a high degree of separation will be less effective for behavioral diffusion than networks in which locally redundant ties are rewired to provide shortcuts across the social space. A competing hypothesis argues that when behaviors require social reinforcement, a network with more clustering may be more advantageous, even if the network as a whole has a larger diameter. I investigated the effects of network structure on diffusion by studying the spread of health behavior through artificially structured online communities. Individual adoption was much more likely when participants received social reinforcement from multiple neighbors in the social network. The behavior spread farther and faster across clustered-lattice networks than across corresponding random networks.


Journal ArticleDOI
16 Apr 2010-Cell
TL;DR: It is shown that amino acids induce the movement of m TORC1 to lysosomal membranes, where the Rag proteins reside, and Rag-Ragulator-mediated translocation of mTORC1 is the key event in amino acid signaling to mtorC1.

Journal ArticleDOI
16 Sep 2010-Nature
TL;DR: It is observed that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates.
Abstract: Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.

Journal ArticleDOI
Thomas J. Hudson1, Thomas J. Hudson2, Warwick Anderson3, Axel Aretz4  +270 moreInstitutions (92)
15 Apr 2010
TL;DR: Systematic studies of more than 25,000 cancer genomes will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
Abstract: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Journal ArticleDOI
29 Oct 2010-Science
TL;DR: A psychometric methodology for quantifying a factor termed “collective intelligence” (c), which reflects how well groups perform on a similarly diverse set of group problem-solving tasks, and finds converging evidence of a general collective intelligence factor that explains a group’s performance on a wide variety of tasks.
Abstract: Psychologists have repeatedly shown that a single statistical factor—often called “general intelligence”— emerges from the correlations among people's performance on a wide variety of cognitive tasks. But no one has systematically examined whether a similar kind of “collective intelligence” exists for groups of people. In two studies with 699 individuals, working in groups of two to five, we find converging evidence of a general collective intelligence factor that explains a group's performance on a wide variety of tasks. This “c factor” is not strongly correlated with the average or maximum individual intelligence of group members but is correlated with the average social sensitivity of group members, the equality in distribution of conversational turn-taking, and the proportion of females in the group. As research, management, and many other kinds of tasks are increasingly accomplished by groups—both those working face-to-face and "virtually"(1‐3)—it is becoming even more important to understand the determinants of group

Journal ArticleDOI
TL;DR: This Review highlights the most important antiviral mechanisms of bacteria as well as the counter-attacks used by phages to evade these systems.
Abstract: Phages are now acknowledged as the most abundant microorganisms on the planet and are also possibly the most diversified. This diversity is mostly driven by their dynamic adaptation when facing selective pressure such as phage resistance mechanisms, which are widespread in bacterial hosts. When infecting bacterial cells, phages face a range of antiviral mechanisms, and they have evolved multiple tactics to avoid, circumvent or subvert these mechanisms in order to thrive in most environments. In this Review, we highlight the most important antiviral mechanisms of bacteria as well as the counter-attacks used by phages to evade these systems.

Journal ArticleDOI
TL;DR: GelMA hydrogels could be useful for creating complex, cell- responsive microtissues, such as endothelialized microvasculature, or for other applications that require cell-responsive microengineered hydrogELs.

01 Jul 2010
TL;DR: The authors showed that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbor residual DNA methylation signatures characteristic of their somatic tissue of origin.
Abstract: Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.

Journal ArticleDOI
TL;DR: In this article, an almost independent constraint on the ratio of distances D-V(0.275) = 0.1390 +/- 0.0037 (2.7 per cent accuracy), where r(s) is the comoving sound horizon at the baryon-drag epoch, DV(z) equivalent to [(1 + z)D(A)(2)cz/H(z)](1/3), D-A(z), is the angular diameter distance and H(z).
Abstract: The spectroscopic Sloan Digital Sky Survey (SDSS) Data Release 7 (DR7) galaxy sample represents the final set of galaxies observed using the original SDSS target selection criteria. We analyse the clustering of galaxies within this sample, including both the luminous red galaxy and main samples, and also include the 2-degree Field Galaxy Redshift Survey data. In total, this sample comprises 893 319 galaxies over 9100 deg(2). Baryon acoustic oscillations (BAO) are observed in power spectra measured for different slices in redshift; this allows us to constrain the distance-redshift relation at multiple epochs. We achieve a distance measure at redshift z = 0.275, of r(s)(z(d))/D-V(0.275) = 0.1390 +/- 0.0037 (2.7 per cent accuracy), where r(s)(z(d)) is the comoving sound horizon at the baryon-drag epoch, D-V(z) equivalent to [(1 + z)(2)D(A)(2)cz/H(z)](1/3), D-A(z) is the angular diameter distance and H(z) is the Hubble parameter. We find an almost independent constraint on the ratio of distances D-V(0.35)/D-V(0.2) = 1.736 +/- 0.065, which is consistent at the 1.1 sigma level with the best-fitting Lambda cold dark matter model obtained when combining our z = 0.275 distance constraint with the Wilkinson Microwave Anisotropy Probe 5-year (WMAP5) data. The offset is similar to that found in previous analyses of the SDSS DR5 sample, but the discrepancy is now of lower significance, a change caused by a revised error analysis and a change in the methodology adopted, as well as the addition of more data. Using WMAP5 constraints on Omega(b)h(2) and Omega(c) h(2), and combining our BAO distance measurements with those from the Union supernova sample, places a tight constraint on Omega(m) = 0.286 +/- 0.018 and H-0 = 68.2 +/- 2.2 km s(-1) Mpc(-1) that is robust to allowing Omega(k) not equal 0 and omega not equal -1. This result is independent of the behaviour of dark energy at redshifts greater than those probed by the BAO and supernova measurements. Combining these data sets with the full WMAP5 likelihood constraints provides tight constraints on both Omega(k) = -0.006 +/- 0.008 and omega = -0.97 +/- 0.10 for a constant dark energy equation of state.