A range of artificial molecular systems has been created that can exhibit controlled linear and rotational motion. In the further development of such systems, a key step is the addition of communication between molecules in a network. Here, we show that a two-dimensional array of dipolar molecular rotors can undergo simultaneous rotational switching when applying an electric field from the tip of a scanning tunnelling microscope. Several hundred rotors made from porphyrin-based double-decker complexes can be simultaneously rotated when in a hexagonal rotor network on a Cu(111) surface by applying biases above 1 V at 80 K. The phenomenon is observed only in a hexagonal rotor network due to the degeneracy of the ground-state dipole rotational energy barrier of the system. Defects are essential to increase electric torque on the rotor network and to stabilize the switched rotor domains. At low biases and low initial rotator angles, slight reorientations of individual rotors can occur, resulting in the rotator arms pointing in different directions. Analysis reveals that the rotator arm directions are not random, but are coordinated to minimize energy via crosstalk among the rotors through dipolar interactions.
Sex determination mechanisms often differ even between related species yet the evolution of sex chromosomes remains poorly understood in all but a few model organisms. Some nematodes such as Caenorhabditis elegans have an XO sex determination system while others, such as the filarial parasite Brugia malayi, have an XY mechanism. We present a complete B. malayi genome assembly and define Nigon elements shared with C. elegans, which we then map to the genomes of other filarial species and more distantly related nematodes. We find a remarkable plasticity in sex chromosome evolution with several distinct cases of neo-X and neo-Y formation, X-added regions, and conversion of autosomes to sex chromosomes from which we propose a model of chromosome evolution across different nematode clades. The phylum Nematoda offers a new and innovative system for gaining a deeper understanding of sex chromosome evolution.
Tbx15 is a member of the T-box gene family of mesodermal developmental genes. We have recently shown that Tbx15 plays a critical role in the formation and metabolic programming of glycolytic myofibers in skeletal muscle. Tbx15 is also differentially expressed among white adipose tissue (WAT) in different body depots. In the current study, using three independent methods, we show that even within a single WAT depot, high Tbx15 expression is restricted to a subset of preadipocytes and mature white adipocytes. Gene expression and metabolic profiling demonstrate that the Tbx15Hi preadipocyte and adipocyte subpopulations of cells are highly glycolytic, whereas Tbx15Low preadipocytes and adipocytes in the same depot are more oxidative and less glycolytic. Likewise, in humans, expression of TBX15 in subcutaneous and visceral WAT is positively correlated with markers of glycolytic metabolism and inversely correlated with obesity. Furthermore, overexpression of Tbx15 is sufficient to reduce oxidative and increase glycolytic metabolism in cultured adipocytes. Thus, Tbx15 differentially regulates oxidative and glycolytic metabolism within subpopulations of white adipocytes and preadipocytes. This leads to a functional heterogeneity of cellular metabolism within WAT that has potential impact in the understanding of human metabolic diseases.
Summary (Abstract)Technologies for measuring 3D genome topology are increasingly important for studying mechanisms of gene regulation, for genome assembly and for mapping of genome rearrangements. Hi-C and other ligation-based methods have become routine but have specific biases. Here, we develop multiplex-GAM, a faster and more affordable version of Genome Architecture Mapping (GAM), a ligation-free technique to map chromatin contacts genomewide. We perform a detailed comparison of contacts obtained by multiplex-GAM and Hi-C using mouse embryonic stem (mES) cells. We find that both methods detect similar topologically associating domains (TADs). However, when examining the strongest contacts detected by either method, we find that only one third of these are shared. The strongest contacts specifically found in GAM often involve “active” regions, including many transcribed genes and super-enhancers, whereas in Hi-C they more often contain “inactive” regions. Our work shows that active genomic regions are involved in extensive complex contacts that currently go under-estimated in genome-wide ligation-based approaches, and highlights the need for orthogonal advances in genome-wide contact mapping technologies.
Context. The blazar 3C 454.3 is one of the most active sources from the radio to the γ-ray frequencies observed in the past few years. Aims. We present multiwavelength observations of this source from April 2008 to March 2010. The radio to optical data are mostly from the GASP-WEBT, UV and X-ray data from Swift, and γ-ray data from the AGILE and Fermi satellites. The aim is to understand the connection among emissions at different frequencies and to derive information on the emitting jet. Methods. Light curves in 18 bands were carefully assembled to study flux variability correlations. We improved the calibration of optical-UV data from the UVOT and OM instruments and estimated the Lyα flux to disentangle the contributions from different components in this spectral region. Results. The observations reveal prominent variability above 8 GHz. In the optical-UV band, the variability amplitude decreases with increasing frequency due to a steadier radiation from both a broad line region and an accretion disc. The optical flux reaches nearly the same levels in the 2008-2009 and 2009-2010 observing seasons; the mm one shows similar behaviour, whereas the γ and X-ray flux levels rise in the second period. Two prominent γ-ray flares in mid 2008 and late 2009 show a double-peaked structure, with a variable γ/optical flux ratio. The X-ray flux variations seem to follow the γ-ray and optical ones by about 0.5 and 1 d, respectively. Conclusions. We interpret the multifrequency behaviour in terms of an inhomogeneous curved jet, where synchrotron radiation of increasing wavelength is produced in progressively outer and wider jet regions, which can change their orientation in time. In particular, we assume that the long-term variability is due to this geometrical effect. By combining the optical and mm light curves to fit the γ and X-ray ones, we find that the γ (X-ray) emission may be explained by inverse-Comptonisation of synchrotron optical (IR) photons by their parent relativistic electrons (SSC process). A slight, variable misalignment between the synchrotron and Comptonisation zones would explain the increased γ and X-ray flux levels in 2009-2010, as well as the change in the γ/optical flux ratio during the outbursts peaks. The time delays of the X-ray flux changes after the γ, and optical ones are consistent with the proposed scenario.
BackgroundRecent epidemiological studies indicate that only 30–50% of undiagnosed type 2 diabetes mellitus (T2DM) patients are identified using glycated hemoglobin (HbA1c) and elevated fasting plasma glucose (FPG) levels. Thus, novel biomarkers for early diagnosis and prognosis are urgently needed for providing early and personalized treatment.MethodsHere, we studied the glycation degrees of 27 glycation sites representing nine plasma proteins in 48 newly diagnosed male T2DM patients and 48 non-diabetic men matched for age (range 35–65 years). Samples were digested with trypsin and enriched for glycated peptides using boronic acid affinity chromatography. Quantification relied on mass spectrometry (multiple reaction monitoring) using isotope-labelled peptides as internal standard.ResultsThe combination of glycated lysine-141 of haptoglobin (HP K141) and HbA1c provided a sensitivity of 94%, a specificity of 98%, and an accuracy of 96% to identify T2DM. A set of 15 features considering three glycation sites in human serum albumin, HP K141, and 11 routine laboratory measures of T2DM, metabolic syndrome, obesity, inflammation, and insulin resistance provided a sensitivity of 98%, a specificity of 100%, and an accuracy of 99% for newly diagnosed T2DM patients.ConclusionsOur studies demonstrated the great potential of glycation sites in plasma proteins providing an additional diagnostic tool for T2DM and elucidating that the combination of these sites with HbA1c and FPG could improve the diagnosis of T2DM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-017-9145-1) contains supplementary material, which is available to authorized users.
We present multiwavelength observations of the ultraluminous blazar-type radio loud quasar PKS 0528+134 in quiescence during the period July to December 2009. Four Target-of-Opportunity (ToO) observations with the XMM-Newton Satellite in the 0.2 -10 keV range were supplemented with optical observations
Recently, the prospects for amorphous phases of graphene (α‐g) have been explored computationally. Initial models were flat, and contained odd‐member rings, while maintaining threefold coordination and sp2 bonding. Upon relaxation, puckering occurs, and may be traced to the existence of pentagons, in analogy with the situation for fullerenes. In this work, we systematically explore the inherent structures with energy close to the flat starting structure. As expected, the planar symmetry can be broken in various ways, which we characterize for 800‐atom model of α‐g, always using local basis density functional techniques. The classical normal modes of various structural models are discussed, with an emphasis on imaginary modes indicating the evolution from flat to puckered. We also discuss very low energy conformational fluctuations akin to those seen previously in amorphous silicon, and reflect on the nature of the amorphous “ground state” within a network of fixed topology. For completeness, high energy modes were also computed, and are found to be associated with strained parts of the network.
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