Showing papers by "Pompeu Fabra University published in 2011"
TL;DR: A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function, and these findings suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Abstract: Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
1,829 citations
TL;DR: Three large-scale neural system models of primate neocortex that emphasize the key contributions of local dynamics, signal transmission delays and noise to the emerging RSNs are reviewed.
Abstract: A broad body of experimental work has demonstrated that apparently spontaneous brain activity is not random. At the level of large-scale neural systems, as measured with functional MRI (fMRI), this ongoing activity reflects the organization of a series of highly coherent functional networks. These so-called resting-state networks (RSNs) closely relate to the underlying anatomical connectivity but cannot be understood in those terms alone. Here we review three large-scale neural system models of primate neocortex that emphasize the key contributions of local dynamics, signal transmission delays and noise to the emerging RSNs. We propose that the formation and dissolution of resting-state patterns reflects the exploration of possible functional network configurations around a stable anatomical skeleton.
1,544 citations
TL;DR: The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease.
Abstract: Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer.
1,435 citations
TL;DR: In this paper, the authors argue that in the presence of intersectoral input-output linkages, microeconomic idiosyncratic shocks may lead to aggregate fluctuations and that the rate at which aggregate volatility decays is determined by the structure of the network capturing such linkages.
Abstract: This paper argues that in the presence of intersectoral input-output linkages, microeconomic idiosyncratic shocks may lead to aggregate fluctuations. In particular, it shows that, as the economy becomes more disaggregated, the rate at which aggregate volatility decays is determined by the structure of the network capturing such linkages. Our main results provide a characterization of this relationship in terms of the importance of different sectors as suppliers to their immediate customers as well as their role as indirect suppliers to chains of downstream sectors. Such higher-order interconnections capture the possibility of “cascade effects” whereby productivity shocks to a sector propagate not only to its immediate downstream customers, but also indirectly to the rest of the economy. Our results highlight that sizable aggregate volatility is obtained from sectoral idiosyncratic shocks only if there exists significant asymmetry in the roles that sectors play as suppliers to others, and that the “sparseness” of the input-output matrix is unrelated to the nature of aggregate fluctuations.
1,174 citations
TL;DR: A new interface for T-Coffee, a consistency-based multiple sequence alignment program, is introduced that provides an easy and intuitive access to the most popular functionality of the package.
Abstract: This article introduces a new interface for T-Coffee, a consistency-based multiple sequence alignment program. This interface provides an easy and intuitive access to the most popular functionality of the package. These include the default T-Coffee mode for protein and nucleic acid sequences, the M-Coffee mode that allows combining the output of any other aligners, and template-based modes of T-Coffee that deliver high accuracy alignments while using structural or homology derived templates. These three available template modes are Expresso for the alignment of protein with a known 3D-Structure, R-Coffee to align RNA sequences with conserved secondary structures and PSI-Coffee to accurately align distantly related sequences using homology extension. The new server benefits from recent improvements of the T-Coffee algorithm and can align up to 150 sequences as long as 10 000 residues and is available from both http:// www.tcoffee.org and its main mirror http://tcoffee .crg.cat.
973 citations
TL;DR: The majority of common small-scale polymorphisms as well as many larger insertions and deletions in the A. thaliana pan-genome are described, their effects on gene function, and the patterns of local and global linkage among these variants.
Abstract: The plant Arabidopsis thaliana occurs naturally in many different habitats throughout Eurasia. As a foundation for identifying genetic variation contributing to adaptation to diverse environments, a 1001 Genomes Project to sequence geographically diverse A. thaliana strains has been initiated. Here we present the first phase of this project, based on population-scale sequencing of 80 strains drawn from eight regions throughout the species' native range. We describe the majority of common small-scale polymorphisms as well as many larger insertions and deletions in the A. thaliana pan-genome, their effects on gene function, and the patterns of local and global linkage among these variants. The action of processes other than spontaneous mutation is identified by comparing the spectrum of mutations that have accumulated since A. thaliana diverged from its closest relative 10 million years ago with the spectrum observed in the laboratory. Recent species-wide selective sweeps are rare, and potentially deleterious mutations are more common in marginal populations.
965 citations
TL;DR: An effective approach to integrating the output of some of these tools into a unified classification is proposed based on a weighted average of the normalized scores of the individual methods (WAS), which shows that this WAS outperforms each individual method in the task of classifying missense SNVs as deleterious or neutral.
Abstract: Several large ongoing initiatives that profit from next-generation sequencing technologies have driven--and in coming years will continue to drive--the emergence of long catalogs of missense single-nucleotide variants (SNVs) in the human genome. As a consequence, researchers have developed various methods and their related computational tools to classify these missense SNVs as probably deleterious or probably neutral polymorphisms. The outputs produced by each of these computational tools are of different natures and thus difficult to compare and integrate. Taking advantage of the possible complementarity between different tools might allow more accurate classifications. Here we propose an effective approach to integrating the output of some of these tools into a unified classification; this approach is based on a weighted average of the normalized scores of the individual methods (WAS). (In this paper, the approach is illustrated for the integration of five tools.) We show that this WAS outperforms each individual method in the task of classifying missense SNVs as deleterious or neutral. Furthermore, we demonstrate that this WAS can be used not only for classification purposes (deleterious versus neutral mutation) but also as an indicator of the impact of the mutation on the functionality of the mutant protein. In other words, it may be used as a deleteriousness score of missense SNVs. Therefore, we recommend the use of this WAS as a consensus deleteriousness score of missense mutations (Condel).
753 citations
TL;DR: The muscle provides a useful model for the regulation of tissue repair by the local microenvironment, showing interplay among muscle-specific stem cells, inflammatory cells, fibroblasts and extracellular matrix components of the mammalian wound-healing response.
Abstract: The repair process of damaged tissue involves the coordinated activities of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells and resident stem cells orchestrate their activities to restore tissue homeostasis. However, during chronic tissue damage, such as in muscular dystrophies, the inflammatory-cell infiltration and fibroblast activation persists, while the reparative capacity of stem cells (satellite cells) is attenuated. Abnormal dystrophic muscle repair and its end stage, fibrosis, represent the final common pathway of virtually all chronic neurodegenerative muscular diseases. As our understanding of the pathogenesis of muscle fibrosis has progressed, it has become evident that the muscle provides a useful model for the regulation of tissue repair by the local microenvironment, showing interplay among muscle-specific stem cells, inflammatory cells, fibroblasts and extracellular matrix components of the mammalian wound-healing response. This article reviews the emerging findings of the mechanisms that underlie normal versus aberrant muscle-tissue repair.
661 citations
TL;DR: How organisms can achieve generic and specific responses to different stresses by regulating gene expression at multiple stages of mRNA biogenesis from chromatin structure to transcription, mRNA stability and translation is discussed.
Abstract: Acute stress puts cells at risk, and rapid adaptation is crucial for maximizing cell survival. Cellular adaptation mechanisms include modification of certain aspects of cell physiology, such as the induction of efficient changes in the gene expression programmes by intracellular signalling networks. Recent studies using genome-wide approaches as well as single-cell transcription measurements, in combination with classical genetics, have shown that rapid and specific activation of gene expression can be accomplished by several different strategies. This article discusses how organisms can achieve generic and specific responses to different stresses by regulating gene expression at multiple stages of mRNA biogenesis from chromatin structure to transcription, mRNA stability and translation.
575 citations
Washington University in St. Louis1, Human Genome Sequencing Center2, University of Oxford3, Wellcome Trust Centre for Human Genetics4, University of Washington5, Pompeu Fabra University6, Howard Hughes Medical Institute7, Wellcome Trust Sanger Institute8, European Bioinformatics Institute9, University of California, Santa Cruz10, University of Illinois at Urbana–Champaign11, Pennsylvania State University12, University of Porto13, Universidade Nova de Lisboa14, University of Bari15, University of Bologna16, Louisiana State University17, Institute for Systems Biology18, Indiana University19, University of Oviedo20, Comenius University in Bratislava21, Cornell University22, Columbia University23, Stanford University24, University of Arizona25, Aarhus University26, Children's Hospital Oakland Research Institute27
TL;DR: The orang-utan species, Pongo abelii and Pongo pygmaeus, are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution and a primate polymorphic neocentromere, found in both Pongo species are described.
Abstract: 'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.
555 citations
TL;DR: A large-scale model of the human brain's neural activity is investigated and it is shown that time-delayed network interaction leads to the emergence of slow neural activity fluctuations, whose patterns correlate significantly with the empirically measured FC.
TL;DR: A uniform definition of unfit patients will lead to more uniform clinical trials, enhanced ability to interpret the results of these trials, and a greater likelihood of developing a viable strategy for regulatory approval.
Abstract: Purpose Cisplatin-based combination chemotherapy is considered standard first-line treatment for patients with metastatic urothelial carcinoma. However, a large proportion of patients with metastatic urothelial carcinoma are considered “unfit” for cisplatin. The purpose of this review is to define unfit patients and to identify treatment options for this subgroup of patients. Patients and Methods In this review, the criteria used to define unfit patients are explored and the results of prospective clinical trials evaluating chemotherapeutic regimens in unfit patients are summarized. Results Several phase II trials and a single, large phase III trial have explored chemotherapeutic regimens for the treatment of unfit patients with metastatic urothelial carcinoma. Heterogeneous eligibility criteria have been used to define unfit patients in these studies. A uniform definition of unfit is proposed on the basis of the results of a survey of genitourinary medical oncologists. According to this definition, unfit...
TL;DR: It is proposed that early deregulation of miR-34b/c in PD triggers downstream transcriptome alterations underlying mitochondrial dysfunction and oxidative stress, which ultimately compromise cell viability.
Abstract: MicroRNAs (miRNAs) are post-transcriptional gene expression regulators, playing key roles in neuronal development, plasticity and disease. Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by the presence of protein inclusions or Lewy bodies and a progressive loss of dopaminergic neurons in the midbrain. Here, we have evaluated miRNA expression deregulation in PD brain samples. MiRNA expression profiling revealed decreased expression of miR-34b and miR-34c in brain areas with variable neuropathological affectation at clinical (motor) stages (Braak stages 4 and 5) of the disease, including the amygdala, frontal cortex, substantia nigra and cerebellum. Furthermore, misregulation of miR-34b/c was detected in pre-motor stages (stages 1-3) of the disease, and thus in cases that did not receive any PD-related treatment during life. Depletion of miR-34b or miR-34c in differentiated SH-SY5Y dopaminergic neuronal cells resulted in a moderate reduction in cell viability that was accompanied by altered mitochondrial function and dynamics, oxidative stress and reduction in total cellular adenosin triphosphate content. MiR-34b/c downregulation was coupled to a decrease in the expression of DJ1 and Parkin, two proteins associated to familial forms of PD that also have a role in idiopathic cases. Accordingly, DJ1 and Parkin expression was reduced in PD brain samples displaying strong miR-34b/c downregulation. We propose that early deregulation of miR-34b/c in PD triggers downstream transcriptome alterations underlying mitochondrial dysfunction and oxidative stress, which ultimately compromise cell viability. A better understanding of the cellular pathways controlling and/or controlled by miR-34b/c should allow identification of targets for development of therapeutic approaches.
TL;DR: The authors used within-country variation in rainfall as a source of transitory shocks to sub-Saharan African economies and found that negative rainfall shocks are followed by significant improvement in democratic institutions.
Abstract: We show that democratic change may be triggered by transitory economic shocks. Our approach uses within-country variation in rainfall as a source of transitory shocks to sub-Saharan African economies. We find that negative rainfall shocks are followed by significant improvement in democratic institutions. This result is consistent with the economic approach to political transitions, where transitory negative shocks can open a window of opportunity for democratic improvement. Instrumental variables estimates indicate that following a transitory negative income shock of 1 percent, democracy scores improve by 0.9 percentage points and the probability of a democratic transition increases by 1.3 percentage points.
TL;DR: It is found that African hunter-gatherer populations today remain highly differentiated, encompassing major components of variation that are not found in other African populations, and tend to have the lowest levels of genome-wide linkage disequilibrium among 27 African populations.
Abstract: Africa is inferred to be the continent of origin for all modern human populations, but the details of human prehistory and evolution in Africa remain largely obscure owing to the complex histories of hundreds of distinct populations. We present data for more than 580,000 SNPs for several hunter-gatherer populations: the Hadza and Sandawe of Tanzania, and the ≠Khomani Bushmen of South Africa, including speakers of the nearly extinct N|u language. We find that African hunter-gatherer populations today remain highly differentiated, encompassing major components of variation that are not found in other African populations. Hunter-gatherer populations also tend to have the lowest levels of genome-wide linkage disequilibrium among 27 African populations. We analyzed geographic patterns of linkage disequilibrium and population differentiation, as measured by FST, in Africa. The observed patterns are consistent with an origin of modern humans in southern Africa rather than eastern Africa, as is generally assumed. Additionally, genetic variation in African hunter-gatherer populations has been significantly affected by interaction with farmers and herders over the past 5,000 y, through both severe population bottlenecks and sex-biased migration. However, African hunter-gatherer populations continue to maintain the highest levels of genetic diversity in the world.
TL;DR: The authors used data on more than 1,000 political leaders between 1875 and 2004 to investigate whether having a more educated leader affects the rate of economic growth and provided evidence supporting the view that heterogeneity among leaders' educational attainment is important with growth being higher by having leaders who are more highly educated.
Abstract: This article uses data on more than 1,000 political leaders between 1875 and 2004 to investigate whether having a more educated leader affects the rate of economic growth. We use an expanded set of random leadership transitions because of natural death or terminal illness to show, following an earlier paper by Jones and Olken (2005), that leaders matter for growth. We then provide evidence supporting the view that heterogeneity among leaders’ educational attainment is important with growth being higher by having leaders who are more highly educated.
TL;DR: The authors analyzes the joint behavior of international capital flows by foreign and domestic agents - gross capital flows - over the business cycle and during financial crises and finds that gross capital flow is very large and volatile, especially relative to net capital flow.
Abstract: This paper analyzes the joint behavior of international capital flows by foreign and domestic agents - gross capital flows - over the business cycle and during financial crises. We show that gross capital flows are very large and volatile, especially relative to net capital flows. When foreigners invest in a country, domestic agents tend to invest abroad, and vice versa. Gross capital flows are also pro-cyclical, with foreigners investing more in the country and domestic agents investing more abroad during expansions. During crises, especially during severe ones, there is retrenchment, that is, a reduction in both capital inflows by foreigners and capital outflows by domestic agents. This evidence sheds light on the nature of shocks driving capital flows and helps discriminate among existing theories. Our findings seem consistent with shocks that affect foreign and domestic agents asymmetrically, such as sovereign risk and asymmetric information.
TL;DR: This paper analyzed the joint behavior of international capital flows by foreign and domestic agents over the business cycle and during financial crises and found that gross capital flows are very large and volatile, especially relative to net capital flows.
TL;DR: It is shown that there is a logically different form of implementing complex Boolean logic computations that reduces wiring constraints thanks to a redundant distribution of the desired output among engineered cells.
Abstract: Ongoing efforts within synthetic and systems biology have been directed towards the building of artificial computational devices using engineered biological units as basic building blocks. Such efforts, inspired in the standard design of electronic circuits, are limited by the difficulties arising from wiring the basic computational units (logic gates) through the appropriate connections, each one to be implemented by a different molecule. Here, we show that there is a logically different form of implementing complex Boolean logic computations that reduces wiring constraints thanks to a redundant distribution of the desired output among engineered cells. A practical implementation is presented using a library of engineered yeast cells, which can be combined in multiple ways. Each construct defines a logic function and combining cells and their connections allow building more complex synthetic devices. As a proof of principle, we have implemented many logic functions by using just a few engineered cells. Of note, small modifications and combination of those cells allowed for implementing more complex circuits such as a multiplexer or a 1-bit adder with carry, showing the great potential for re-utilization of small parts of the circuit. Our results support the approach of using cellular consortia as an efficient way of engineering complex tasks not easily solvable using single-cell implementations.
TL;DR: It is demonstrated for the first time that a consistent reduction of a biophysically realistic spiking network of leaky integrate-and-fire neurons with spike-frequency adaptation could account for binocular rivalry.
Abstract: Perceptual bistability arises when two conflicting interpretations of an ambiguous stimulus or images in binocular rivalry (BR) compete for perceptual dominance. From a computational point of view competition models based on cross-inhibition and adaptation have shown that noise is a crucial force for rivalry and operates in balance with adaptation in order to explain the observed alternations in perception. In particular, noise-driven transitions and adaptation-driven oscillations define two dynamical regimes and the system operates near its boundary. In order to gain insights into the microcircuit dynamics mediating spontaneous perceptual alternations we used a reduced recurrent attractor-based biophysically realistic spiking network well known for working memory, attention and decision-making, where a spike-frequency adaptation mechanism is implemented to account for perceptual bistability. We, thus, derived a consistently reduced four-variable population rate model using mean-field techniques and tested it on BR data collected from human subjects. Our model accounts for experimental data parameters such as time dominance, coefficient of variation and gamma distribution. In addition, we show that our model also operates on the boundary between noise and adaptation and agrees with Levelt’s second revised and fourth propositions. These results show for the first time that a consistent reduction of a biophysically realistic spiking network of integrate and fire neurons with spike frequency adaptation could account for BR. Moreover, we demonstrate that BR can be explained only through the dynamics of the competing neuronal pools, without taking into account the adaptation of inhibitory interneurons..However, adaptation of interneurons affects the optimal parametric space of the system, by decreasing the overall adaptation necessary for the bifurcation to occur.
TL;DR: In this paper, the authors proposed new methodologies for evaluating economic models' out-of-sample forecasting performance that are robust to the choice of the estimation window size, and evaluated the predictive ability of forecasting models over a wide range of window sizes.
Abstract: This article proposes new methodologies for evaluating economic models’ out-of-sample forecasting performance that are robust to the choice of the estimation window size. The methodologies involve evaluating the predictive ability of forecasting models over a wide range of window sizes. The study shows that the tests proposed in the literature may lack the power to detect predictive ability and might be subject to data snooping across different window sizes if used repeatedly. An empirical application shows the usefulness of the methodologies for evaluating exchange rate models’ forecasting ability.
TL;DR: An overview of the current understanding of the molecular mechanisms that can cause epistasis, and areas where more research is needed are provided.
TL;DR: The authors assesses to what extent do these forms of digital discussion fit in Habermas' principles for democratic debate, using his discursive ethics as a demanding normative benchmark, and two models of audience participation emerge from the analysis, one where communities of debate are formed based on mostly respectful discussions between diverse points of view and another of homogenous communities, in which expres...
Abstract: Comments in online news could be the contemporary enactment of the eighteenth-century cafes that founded public sphere. This article assesses to what extent do these forms of digital discussion fit in Habermas’ principles for democratic debate, using his discursive ethics as a demanding normative benchmark. The sample of more than 15,000 comments was selected from the online versions of five national newspapers of record from different political and journalistic contexts: The Guardian (United Kingdom), Le Monde (France), The New York Times (United States), El Pais (Spain), and La Repubblica (Italy). The ethical guidelines and legal frameworks set up by the newspapers as well as their moderation strategies were considered to understand the different settings of the conversations. Two models of audience participation emerge from the analysis, one where communities of debate are formed based on mostly respectful discussions between diverse points of view and another of homogenous communities, in which expres...
TL;DR: Predictions of interactions between PRC2 protein components and HOTAIR regions and comparisons between catRAPID predictions and experimental data are shown.
Abstract: Supplementary Figure 4 Predictions of interactions between PRC2 protein components and HOTAIR regions Supplementary Table 1 PDB IDs of non-redundant protein-RNA complexes used to train catRAPID Supplementary Table 2 Coefficients associated with protein and RNA properties Supplementary Table 3 Parameters of the interaction matrix I Supplementary Table 4 Composition of the NPInter dataset Supplementary Table 5 Composition of the Protein-binding (Protein BP), DNAbinding, RNA-binding (RNA BP) datasets Supplementary Table 6 Human MRP complex: Comparison between catRAPID predictions and experimental data Supplementary Methods
TL;DR: Recent advances in the production of taxol and related taxanes in Taxus baccata, the taxol-producing European yew, using cell suspension culture technology are focused on, giving particular emphasis to the optimization steps that have improved production and including the most recently developed new tools.
TL;DR: Evidence that spontaneous, that is, not stimulus or task driven, activity in the brain at the level of large-scale neural systems is not noise, but orderly and organized in a series of functional networks that maintain, at all times, a high level of coherence is reviewed.
Abstract: The authors review evidence that spontaneous, that is, not stimulus or task driven, activity in the brain at the level of large-scale neural systems is not noise, but orderly and organized in a series of functional networks that maintain, at all times, a high level of coherence. These networks of spontaneous activity correlation or resting state networks (RSN) are closely related to the underlying anatomical connectivity, but their topography is also gated by the history of prior task activation. Network coherence does not depend on covert cognitive activity, but its strength and integrity relates to behavioral performance. Some RSN are functionally organized as dynamically competing systems both at rest and during tasks. Computational studies show that one of such dynamics, the anticorrelation between networks, depends on noise-driven transitions between different multistable cluster synchronization states. These multistable states emerge because of transmission delays between regions that are modeled as coupled oscillators systems. Large-scale systems dynamics are useful for keeping different functional subnetworks in a state of heightened competition, which can be stabilized and fired by even small modulations of either sensory or internal signals.
TL;DR: In this paper, the standard New Keynesian model with a staggered wage setting is shown to imply a simple dynamic relation between wage inflation and unemployment, and that relation takes a form similar to that found in empirical applications and may thus be viewed as providing some theoretical foundations to the latter.
Abstract: The standard New Keynesian model with staggered wage setting is shown to imply a simple dynamic relation between wage inflation and unemployment. Under some assumptions, that relation takes a form similar to that found in empirical applications -starting with the original Phillips (1958) curve- and may thus be viewed as providing some theoretical foundations to the latter. The structural wage equation derived here is shown to account reasonably well for the comovement of wage inflation and the unemployment rate in the U.S. economy, even under the strong assumption of a constant natural rate of unemployment.
TL;DR: Dorsal and ventral striatum are proposed to compute outcome predictions largely in parallel, using different types of information as input, and the specificity of predictions transcends the level of scalar value signals, incorporating episodic information.
TL;DR: In this paper, the exomes of three individuals with Bohring-Opitz syndrome were sequenced and each identified heterozygous de novo nonsense mutations in ASXL1, which is required for maintenance of both activation and silencing of Hox genes.
Abstract: Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which is required for maintenance of both activation and silencing of Hox genes. In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous.
TL;DR: Results indicate that Snail1 controls Zeb1 expression at multiple levels and acts cooperatively with Twist in the ZEB1 gene transcription induction, showing a mutual dependence although to a different extent.