288 research outputs found
Formation of regulatory modules by local sequence duplication
Turnover of regulatory sequence and function is an important part of
molecular evolution. But what are the modes of sequence evolution leading to
rapid formation and loss of regulatory sites? Here, we show that a large
fraction of neighboring transcription factor binding sites in the fly genome
have formed from a common sequence origin by local duplications. This mode of
evolution is found to produce regulatory information: duplications can seed new
sites in the neighborhood of existing sites. Duplicate seeds evolve
subsequently by point mutations, often towards binding a different factor than
their ancestral neighbor sites. These results are based on a statistical
analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome,
and a comparison set of intergenic regulatory sequence in Saccharomyces
cerevisiae. In fly regulatory modules, pairs of binding sites show
significantly enhanced sequence similarity up to distances of about 50 bp. We
analyze these data in terms of an evolutionary model with two distinct modes of
site formation: (i) evolution from independent sequence origin and (ii)
divergent evolution following duplication of a common ancestor sequence. Our
results suggest that pervasive formation of binding sites by local sequence
duplications distinguishes the complex regulatory architecture of higher
eukaryotes from the simpler architecture of unicellular organisms
A quantum spin transducer based on nano electro-mechancial resonator arrays
Implementation of quantum information processing faces the contradicting
requirements of combining excellent isolation to avoid decoherence with the
ability to control coherent interactions in a many-body quantum system. For
example, spin degrees of freedom of electrons and nuclei provide a good quantum
memory due to their weak magnetic interactions with the environment. However,
for the same reason it is difficult to achieve controlled entanglement of spins
over distances larger than tens of nanometers. Here we propose a universal
realization of a quantum data bus for electronic spin qubits where spins are
coupled to the motion of magnetized mechanical resonators via magnetic field
gradients. Provided that the mechanical system is charged, the magnetic moments
associated with spin qubits can be effectively amplified to enable a coherent
spin-spin coupling over long distances via Coulomb forces. Our approach is
applicable to a wide class of electronic spin qubits which can be localized
near the magnetized tips and can be used for the implementation of hybrid
quantum computing architectures
Normative values for the Foot Posture Index
This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
On the Implications of a Sex Difference in the Reaction Times of Sprinters at the Beijing Olympics
Elite sprinters offer insights into the fastest whole body auditory reaction times. When, however, is a reaction so fast that it represents a false start? Currently, a false start is awarded if an athlete increases the force on their starting block above a given threshold before 100 ms has elapsed after the starting gun. To test the hypothesis that the fastest valid reaction times of sprinters really is 100 ms and that no sex difference exists in that time, we analyzed the fastest reaction times achieved by each of the 425 male and female sprinters who competed at the 2008 Beijing Olympics. After power transformation of the skewed data, a fixed effects ANOVA was used to analyze the effects of sex, race, round and lane position. The lower bounds of the 95, 99 and 99.9% confidence intervals were then calculated and back transformed. The mean fastest reaction time recorded by men was significantly faster than women (p<0.001). At the 99.9% confidence level, neither men nor women can react in 100 ms, but they can react in as little as 109 ms and 121 ms, respectively. However, that sex difference in reaction time is likely an artifact caused by using the same force threshold in women as men, and it permits a woman to false start by up to 21 ms without penalty. We estimate that female sprinters would have similar reaction times to male sprinters if the force threshold used at Beijing was lowered by 22% in order to account for their lesser muscle strength
Entering a new era of body indices: the feasibility of a body shape index and body roundness index to identify cardiovascular health status.
BACKGROUND: The Body Mass Index (BMI) and Waist Circumference (WC) are well-used anthropometric predictors for cardiovascular diseases (CVD), but their validity is regularly questioned. Recently, A Body Shape Index (ABSI) and Body Roundness Index (BRI) were introduced as alternative anthropometric indices that may better reflect health status. OBJECTIVE: This study assessed the capacity of ABSI and BRI in identifying cardiovascular diseases and cardiovascular disease risk factors and determined whether they are superior to BMI and WC. DESIGN AND METHODS: 4627 Participants (54±12 years) of the Nijmegen Exercise Study completed an online questionnaire concerning CVD health status (defined as history of CVD or CVD risk factors) and anthropometric characteristics. Quintiles of ABSI, BRI, BMI, and WC were used regarding CVD prevalence. Odds ratios (OR), adjusted for age, sex, and smoking, were calculated per anthropometric index. RESULTS: 1332 participants (27.7%) reported presence of CVD or CVD risk factors. The prevalence of CVD increased across quintiles for BMI, ABSI, BRI, and WC. Comparing the lowest with the highest quintile, adjusted OR (95% CI) for CVD were significantly different for BRI 3.2 (1.4-7.2), BMI 2.4 (1.9-3.1), and WC 3.0 (1.6-5.6). The adjusted OR (95% CI) for CVD risk factors was for BRI 2.5 (2.0-3.3), BMI 3.3 (1.6-6.8), and WC 2.0 (1.6-2.5). No association was observed for ABSI in both groups. CONCLUSIONS: BRI, BMI, and WC are able to determine CVD presence, while ABSI is not capable. Nevertheless, the capacity of BRI as a novel body index to identify CVD was not superior compared to established anthropometric indices like BMI and WC
Control over topological insulator photocurrents with light polarization
Three-dimensional topological insulators represent a new quantum phase of
matter with spin-polarized surface states that are protected from
backscattering. The static electronic properties of these surface states have
been comprehensively imaged by both photoemission and tunneling spectroscopies.
Theorists have proposed that topological surface states can also exhibit novel
electronic responses to light, such as topological quantum phase transitions
and spin-polarized electrical currents. However, the effects of optically
driving a topological insulator out of equilibrium have remained largely
unexplored experimentally, and no photocurrents have been measured. Here we
show that illuminating the topological insulator Bi2Se3 with circularly
polarized light generates a photocurrent that originates from topological
helical Dirac fermions, and that reversing the helicity of the light reverses
the direction of the photocurrent. We also observe a photocurrent that is
controlled by the linear polarization of light, and argue that it may also have
a topological surface state origin. This approach may allow the probing of
dynamic properties of topological insulators and lead to novel opto-spintronic
devices.Comment: Accepted in Nature Nanotechnology, November 2 201
Disorders of compulsivity: a common bias towards learning habits.
Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.This study was funded by the WT fellowship grant for VV (093705/Z/
10/Z) and Cambridge NIHR Biomedical Research Centre. VV and NAH are Wellcome
Trust (WT) intermediate Clinical Fellows. YW is supported by the Fyssen Fondation
and MRC Studentships. PD is supported by the Gatsby Charitable Foundation. JEG has
received grants from the National Institute of Drug Abuse and the National Center for
Responsible Gaming. TWR and BJS are supported on a WT Programme Grant
(089589/Z/09/Z). The BCNI is supported by a WT and MRC grant.This is the final published version. It's also available from Molecular Psychiatry at http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201444a.html
Rapid generation of human B-cell lymphomas via combined expression of Myc and Bcl2 and their use as a preclinical model for biological therapies
Although numerous mouse models of B-cell malignancy have been developed via the enforced expression of defined oncogenic lesions, the feasibility of generating lineage-defined human B-cell malignancies using mice reconstituted with modified human hematopoietic stem cells (HSCs) remains unclear. In fact, whether human cells can be transformed as readily as murine cells by simple oncogene combinations is a subject of considerable debate. Here, we describe the development of humanized mouse model of MYC/BCL2-driven ‘double-hit’ lymphoma. By engrafting human HSCs transduced with the oncogene combination into immunodeficient mice, we generate a fatal B malignancy with complete penetrance. This humanized-MYC/BCL2-model (hMB) accurately recapitulates the histopathological and clinical aspects of steroid-, chemotherapy- and rituximab-resistant human ‘double-hit’ lymphomas that involve the MYC and BCL2 loci. Notably, this model can serve as a platform for the evaluation of antibody-based therapeutics. As a proof of principle, we used this model to show that the anti-CD52 antibody alemtuzumab effectively eliminates lymphoma cells from the spleen, liver and peripheral blood, but not from the brain. The hMB humanized mouse model underscores the synergy of MYC and BCL2 in ‘double-hit’ lymphomas in human patients. Additionally, our findings highlight the utility of humanized mouse models in interrogating therapeutic approaches, particularly human-specific monoclonal antibodies.Kathy and Curt Marble Cancer Research FundSingapore-MIT Alliance for Research and TechnologyNational Institutes of Health (U.S.) (Grant R01-CA128803)Virginia and Daniel K. Ludwig Graduate FellowshipNational Institute of General Medical Sciences (U.S.) (Medical Scientist Training Program Grant T32GM007753)MIT School of Science (Cancer Research Fellowship
Dynamic Activation and Repression of the Plasmodium falciparum rif Gene Family and Their Relation to Chromatin Modification
The regulation of variant gene expression in Plasmodium falciparum is still only partially understood. Regulation of var genes, the most studied gene family involved in antigenic variation, is orchestrated by a dynamic pattern of inherited chromatin states. Although recent evidence pointed to epigenetic regulation of transcribed and repressed rif loci, little is known about specific on/off associated histone modifications of individual rif genes. To investigate the chromatin marks for transcribed and repressed rif loci, we cultivated parasites and evaluated the transcriptional status of chosen rif targets by qRT-PCR and performed ChIP assays using H3K9ac and H3K9me3 antibodies. We then monitored changes in the epigenetic patterns in parasites after several reinvasions and also evaluated the “poised” mark in trophozoites and schizonts of the same erythrocytic cycle by ChIP using H3K4me2 specific antibodies. Our results show that H3K9 is acetylated in transcribed rif loci and trimethylated or even unmodified in repressed rif loci. These transcriptional and epigenetic states are inherited after several reinvasions. The poised modification H3K4me2 showed a tendency to be more present in loci in trophozoites that upon progression to schizonts strongly transcribe the respective locus. However, this effect was not consistently observed for all monitored loci. While our data show important similarities to var transcription-associated chromatin modifications, the observed swiftly occurring modifications at rif loci and the absence of H3K9 modification point to a different dynamic of recruitment of chromatin modifying enzymes
Comparing regional organizations in global multilateral institutions:ASEAN, the EU and the UN
Structural change brought about by the end of the Cold War and accelerated globalisation have transformed the global environment. A global governance complex is emerging, characterised by an ever-greater functional and regulatory role for multilateral organisations such as the United Nations (UN) and its associated agencies. The evolving global governance framework has created opportunities for regional organisations to participate as actors within the UN (and other multilateral institutions). This article compares the European Union (EU) and Association of Southeast Asian Nations (ASEAN) as actors within the UN network. It begins by extrapolating framework conditions for the emergence of EU and ASEAN actorness from the literature. The core argument of this article is that EU and ASEAN actorness is evolving in two succinct stages: Changes in the global environment create opportunities for the participation of regional organisations in global governance institutions, exposing representation and cohesion problems at the regional level. In response, ASEAN and the EU have initiated processes of institutional adaptation
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