Multigenome DNA sequence conservation identifies Hox cis-regulatory elements

To learn how well ungapped sequence comparisons of multiple species can predict cis-regulatory elements in Caenorhabditis elegans, we made such predictions across the large, complex ceh-13/lin-39 locus and tested them transgenically. We also examined how prediction quality varied with different genomes and parameters in our comparisons. Specifically, we sequenced ∼0.5% of the C. brenneri and C. sp. 3 PS1010 genomes, and compared five Caenorhabditis genomes (C. elegans, C. briggsae, C. brenneri, C. remanei, and C. sp. 3 PS1010) to find regulatory elements in 22.8 kb of noncoding sequence from the ceh-13/lin-39 Hox subcluster. We developed the MUSSA program to find ungapped DNA sequences with N-way transitive conservation, applied it to the ceh-13/lin-39 locus, and transgenically assayed 21 regions with both high and low degrees of conservation. This identified 10 functional regulatory elements whose activities matched known ceh-13/lin-39 expression, with 100% specificity and a 77% recovery rate. One element was so well conserved that a similar mouse Hox cluster sequence recapitulated the native nematode expression pattern when tested in worms. Our findings suggest that ungapped sequence comparisons can predict regulatory elements genome-wide

Improved Thermal-Vacuum Compatible Flat Plate Radiometric Souce for System-Level Testing of Optical Sensors

This work describes the development of an improved vacuum compatible flat plate radiometric source used for characterizing and calibrating remote optical sensors, in situ, throughout their testing period. The original flat plate radiometric source was developed for use by the VIIRS instrument during the NPOESS Preparatory Project (NPP). Following this effort, the FPI has had significant upgrades in order to improve both the radiometric throughput and uniformity. Results of the VIIRS testing with the reconfigured FPI are reported and discussed

Social complexity in bees is not sufficient to explain lack of reversions to solitary living over long time scales

BackgroundThe major lineages of eusocial insects, the ants, termites, stingless bees, honeybees and vespid wasps, all have ancient origins (> or = 65 mya) with no reversions to solitary behaviour. This has prompted the notion of a 'point of no return' whereby the evolutionary elaboration and integration of behavioural, genetic and morphological traits over a very long period of time leads to a situation where reversion to solitary living is no longer an evolutionary option.ResultsWe show that in another group of social insects, the allodapine bees, there was a single origin of sociality > 40 mya. We also provide data on the biology of a key allodapine species, Halterapis nigrinervis, showing that it is truly social. H. nigrinervis was thought to be the only allodapine that was not social, and our findings therefore indicate that there have been no losses of sociality among extant allodapine clades. Allodapine colony sizes rarely exceed 10 females per nest and all females in virtually all species are capable of nesting and reproducing independently, so these bees clearly do not fit the 'point of no return' concept.ConclusionWe argue that allodapine sociality has been maintained by ecological constraints and the benefits of alloparental care, as opposed to behavioural, genetic or morphological constraints to independent living. Allodapine brood are highly vulnerable to predation because they are progressively reared in an open nest (not in sealed brood cells), which provides potentially large benefits for alloparental care and incentives for reproductives to tolerate potential alloparents. We argue that similar vulnerabilities may also help explain the lack of reversions to solitary living in other taxa with ancient social origins.Luke B. Chenoweth, Simon M. Tierney, Jaclyn A. Smith, Steven J.B. Cooper and Michael P. Schwar

Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied in relation to the glutamate hypothesis of schizophrenia and increases dissociation, positive and negative symptom ratings. Ketamine effects brain function through changes in brain activity; these activity patterns can be modulated by pre-treatment of compounds known to attenuate the effects of ketamine on glutamate release. Ketamine also has marked effects on brain connectivity; we predicted that these changes would also be modulated by compounds known to attenuate glutamate release. Here, we perform task-free pharmacological magnetic resonance imaging (phMRI) to investigate the functional connectivity effects of ketamine in the brain and the potential modulation of these effects by pre-treatment of the compounds lamotrigine and risperidone, compounds hypothesised to differentially modulate glutamate release. Connectivity patterns were assessed by combining windowing, graph theory and multivariate Gaussian process classification. We demonstrate that ketamine has a robust effect on the functional connectivity of the human brain compared to saline (87.5 % accuracy). Ketamine produced a shift from a cortically centred, to a subcortically centred pattern of connections. This effect is strongly modulated by pre-treatment with risperidone (81.25 %) but not lamotrigine (43.75 %). Based on the differential effect of these compounds on ketamine response, we suggest the observed connectivity effects are primarily due to NMDAR blockade rather than downstream glutamatergic effects. The connectivity changes contrast with amplitude of response for which no differential effect between pre-treatments was detected, highlighting the necessity of these techniques in forming an informed view of the mechanistic effects of pharmacological compounds in the human brain

Damping of Tensor Modes in Cosmology

An analytic formula is given for the traceless transverse part of the anisotropic stress tensor due to free streaming neutrinos, and used to derive an integro-differential equation for the propagation of cosmological gravitational waves. The solution shows that anisotropic stress reduces the squared amplitude by 35.6 % for wavelengths that enter the horizon during the radiation-dominated phase, independent of any cosmological parameters. This decreases the tensor temperature and polarization correlation functions for these wavelengths by the same amount. The effect is less for wavelengths that enter the horizon at later times. At the longest wavelengths the decrease in the tensor correlation functions due to neutrino free streaming ranges from 10.7% for $\Omega_Mh^2=0.1$ to 9.0% for $\Omega_Mh^2=0.15$. An Appendix gives a general proof that tensor as well as scalar modes satisfy a conservation law for perturbations outside the horizon, even when the anisotropic stress tensor is not negligible.Comment: 14 pages. The original version of this paper has been expanded to deal with perturbations of any wavelength. While for wavelengths short enough to enter the horizon during radiation dominance, temperature and polarization correlations are damped by 35.6%, at the longest wavelengths the damping is from 9.0% to 11%. An added Appendix gives a general proof that tensor as well as scalar modes satisfy a conservation law outside the horizon, even during neutrino decoupling. Some references are also adde

Severe Obstructive Sleep Apnea Disrupts Vigilance-State-Dependent Metabolism

The direct pathophysiological effects of obstructive sleep apnea (OSA) have been well described. However, the systemic and metabolic consequences of OSA are less well understood. The aim of this secondary analysis was to translate recent findings in healthy subjects on vigilance-state-dependent metabolism into the context of OSA patients and answer the question of how symptomatic OSA influences metabolism and whether these changes might explain metabolic and cardiovascular consequences of OSA. Patients with suspected OSA were assigned according to their oxygen desaturation index (ODI) and Epworth Sleepiness Scale (ESS) score into symptomatic OSA and controls. Vigilance-state-dependent breath metabolites assessed by high-resolution mass spectrometry were used to test for a difference in both groups. In total, 44 patients were eligible, of whom 18 (40.9%) were assigned to the symptomatic OSA group. Symptomatic OSA patients with a median [25%, 75% quartiles] ODI of 40.5 [35.0, 58.8] events/h and an ESS of 14.0 [11.2, 15.8] showed moderate to strong evidence for differences in 18 vigilance-state-dependent breath compounds compared to controls. These identified metabolites are part of major metabolic pathways in carbohydrate, amino acid, and lipid metabolism. Thus, beyond hypoxia per se, we hypothesize that disturbed sleep in OSA patients persists as disturbed sleep-dependent metabolite levels during daytime

Baryons and Domain Walls in an N = 1 Superconformal Gauge Theory

Coincident D3-branes placed at a conical singularity are related to string theory on $AdS_5\times X_5$, for a suitable five-dimensional Einstein manifold $X_5$. For the example of the conifold, which leads to $X_5=T^{1,1}=(SU(2)\times SU(2))/U(1)$, the infrared limit of the theory on $N$ D3-branes was constructed recently. This is ${\cal N}=1$ supersymmetric $SU(N)\times SU(N)$ gauge theory coupled to four bifundamental chiral superfields and supplemented by a quartic superpotential which becomes marginal in the infrared. In this paper we consider D3-branes wrapped over the 3-cycles of $T^{1,1}$ and identify them with baryon-like chiral operators built out of products of $N$ chiral superfields. The supergravity calculation of the dimensions of such operators agrees with field theory. We also study the D5-brane wrapped over a 2-cycle of $T^{1,1}$, which acts as a domain wall in $AdS_5$. We argue that upon crossing it the gauge group changes to $SU(N)\times SU(N+1)$. This suggests a construction of supergravity duals of ${\cal N}=1$ supersymmetric $SU(N_1)\times SU(N_2)$ gauge theories.Comment: 14 pages, latex; v2: discussion at the end of section 3 modified, the version to appear in Physical Review

Coupling Constant Dependence in the Thermodynamics of N=4 Supersymmetric Yang-Mills Theory

The free energy of the maximally supersymmetric SU(N) gauge theory at temperature T is expected to scale, in the large N limit, as N^2 T^4 times a function of the 't Hooft coupling, f(g_{YM}^2 N). In the strong coupling limit the free energy has been deduced from the near-extremal 3-brane geometry, and its normalization has turned out to be 3/4 times that found in the weak coupling limit. In this paper we calculate the leading correction to this result in inverse powers of the coupling, which originates from the R^4 terms in the tree level effective action of type IIB string theory. The correction to 3/4 is positive and of order (g_{YM}^2 N)^{-3/2}. Thus, f(g_{YM}^2 N) increases as the 't Hooft coupling is decreased, in accordance with the expectation that it should be approaching 1 in the weak coupling limit. We also discuss similar corrections for other conformal theories describing coincident branes. In particular, we suggest that the coupling-independence of the near extremal entropy for D1-branes bound to D5-branes is related to the vanishing of the Weyl tensor of AdS_3\times S^3.Comment: 24 pages; a paragraph about the 5-form background added in section 3; in the Note Added we clarify the meaning of the metric found in section 3; sign in eq. (34) correcte

Hierarchies from Fluxes in String Compactifications

Warped compactifications with significant warping provide one of the few known mechanisms for naturally generating large hierarchies of physical scales. We demonstrate that this mechanism is realizable in string theory, and give examples involving orientifold compactifications of IIB string theory and F-theory compactifications on Calabi-Yau four-folds. In each case, the hierarchy of scales is fixed by a choice of RR and NS fluxes in the compact manifold. Our solutions involve compactifications of the Klebanov-Strassler gravity dual to a confining N=1 supersymmetric gauge theory,and the hierarchy reflects the small scale of chiral symmetry breaking in the dual gauge theory.Comment: 35 pages. v2: minor eqn. and reference change

Possible detection of two giant extrasolar planets orbiting the eclipsing polar UZ Fornacis

We present new high-speed, multi-observatory, multi-instrument photometry of the eclipsing polar UZ For in order to measure precise mid-eclipse times with the aim of detecting any orbital period variations. When combined with published eclipse times and archival data spanning ~27 years, we detect departures from a linear and quadratic trend of ~60 s. The departures are strongly suggestive of two cyclic variations of 16(3) and 5.25(25) years. The two favoured mechanisms to drive the periodicities are either two giant extrasolar planets as companions to the binary (with minimum masses of 6.3(1.5)M(Jupiter) and 7.7(1.2)M(Jupiter)) or a magnetic cycle mechanism (e.g. Applegate's mechanism) of the secondary star. Applegate's mechanism would require the entire radiant energy output of the secondary and would therefore seem to be the least likely of the two, barring any further refinements in the effect of magnetic fieilds (e.g. those of Lanza et al.). The two planet model can provide realistic solutions but it does not quite capture all of the eclipse times measurements. A highly eccentric orbit for the outer planet would fit the data nicely, but we find that such a solution would be unstable. It is also possible that the periodicities are driven by some combination of both mechanisms. Further observations of this system are encouraged.Comment: 10 pages, 4 figures, 2 table