Targeted Derepression of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat by Pyrrole-Imidazole Polyamides

The host factor LSF represses the human immunodeficiency virus type 1 long terminal repeat (LTR) by mediating recruitment of histone deacetylase. We show that pyrrole-imidazole polyamides targeted to the LTR can specifically block LSF binding both in vitro and within cells via direct access to chromatin, resulting in increased LTR expression

Arrested Cracks in Nonlinear Lattice Models of Brittle Fracture

We generalize lattice models of brittle fracture to arbitrary nonlinear force laws and study the existence of arrested semi-infinite cracks. Unlike what is seen in the discontinuous case studied to date, the range in driving displacement for which these arrested cracks exist is very small. Also, our results indicate that small changes in the vicinity of the crack tip can have an extremely large effect on arrested cracks. Finally, we briefly discuss the possible relevance of our findings to recent experiments.Comment: submitted to PRE, Rapid Communication

The visual perception of natural motion: abnormal task-related neural activity in DYT1 dystonia

Although primary dystonia is defined by its characteristic motor manifestations, non-motor signs and symptoms have increasingly been recognized in this disorder. Recent neuroimaging studies have related the motor features of primary dystonia to connectivity changes in cerebello-thalamo-cortical pathways. It is not known, however, whether the non-motor manifestations of the disorder are associated with similar circuit abnormalities. To explore this possibility, we used functional magnetic resonance imaging to study primary dystonia and healthy volunteer subjects while they performed a motion perception task in which elliptical target trajectories were visually tracked on a computer screen. Prior functional magnetic resonance imaging studies of healthy subjects performing this task have revealed selective activation of motor regions during the perception of \u27natural\u27 versus \u27unnatural\u27 motion (defined respectively as trajectories with kinematic properties that either comply with or violate the two-thirds power law of motion). Several regions with significant connectivity changes in primary dystonia were situated in proximity to normal motion perception pathways, suggesting that abnormalities of these circuits may also be present in this disorder. To determine whether activation responses to natural versus unnatural motion in primary dystonia differ from normal, we used functional magnetic resonance imaging to study 10 DYT1 dystonia and 10 healthy control subjects at rest and during the perception of \u27natural\u27 and \u27unnatural\u27 motion. Both groups exhibited significant activation changes across perceptual conditions in the cerebellum, pons, and subthalamic nucleus. The two groups differed, however, in their responses to \u27natural\u27 versus \u27unnatural\u27 motion in these regions. In healthy subjects, regional activation was greater during the perception of natural (versus unnatural) motion (P \u3c 0.05). By contrast, in DYT1 dystonia subjects, activation was relatively greater during the perception of unnatural (versus natural) motion (P \u3c 0.01). To explore the microstructural basis for these functional changes, the regions with significant interaction effects (i.e. those with group differences in activation across perceptual conditions) were used as seeds for tractographic analysis of diffusion tensor imaging scans acquired in the same subjects. Fibre pathways specifically connecting each of the significant functional magnetic resonance imaging clusters to the cerebellum were reconstructed. Of the various reconstructed pathways that were analysed, the ponto-cerebellar projection alone differed between groups, with reduced fibre integrity in dystonia (P \u3c 0.001). In aggregate, the findings suggest that the normal pattern of brain activation in response to motion perception is disrupted in DYT1 dystonia. Thus, it is unlikely that the circuit changes that underlie this disorder are limited to primary sensorimotor pathways

Altering Pyrroloquinoline Quinone Nutritional Status Modulates Mitochondrial, Lipid, and Energy Metabolism in Rats

We have reported that pyrroloquinoline quinone (PQQ) improves reproduction, neonatal development, and mitochondrial function in animals by mechanisms that involve mitochondrial related cell signaling pathways. To extend these observations, the influence of PQQ on energy and lipid relationships and apparent protection against ischemia reperfusion injury are described herein. Sprague-Dawley rats were fed a nutritionally complete diet with PQQ added at either 0 (PQQ−) or 2 mg PQQ/Kg diet (PQQ+). Measurements included: 1) serum glucose and insulin, 2) total energy expenditure per metabolic body size (Wt3/4), 3) respiratory quotients (in the fed and fasted states), 4) changes in plasma lipids, 5) the relative mitochondrial amount in liver and heart, and 6) indices related to cardiac ischemia. For the latter, rats (PQQ− or PQQ+) were subjected to left anterior descending occlusions followed by 2 h of reperfusion to determine PQQ's influence on infarct size and myocardial tissue levels of malondialdehyde, an indicator of lipid peroxidation. Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ− vs. PQQ+ rats and energy expenditure (fed state) was correlated with the hepatic mitochondrial content. Elevations in plasma di- and triacylglyceride and β-hydroxybutryic acid concentrations were also observed in PQQ− rats vs. PQQ+ rats. Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days) resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes. Cardiac injury resulting from ischemia/reperfusion was more pronounced in PQQ− rats than in PQQ+ rats. Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function

Novel critical point drying (CPD) based preparation and transmission electron microscopy (TEM) imaging of protein specific molecularly imprinted polymers (HydroMIPs)

We report the transmission electron microscopy (TEM) imaging of a hydrogel-based molecularly imprinted polymer (HydroMIP) specific to the template molecule bovine haemoglobin (BHb). A novel critical point drying based sample preparation technique was employed to prepare the molecularly imprinted polymer (MIP) samples in a manner that would facilitate the use of TEM to image the imprinted cavities, and provide an appropriate degree of both magnification and resolution to image polymer architecture in the <10 nm range. For the first time, polymer structure has been detailed that clearly displays molecularly imprinted cavities, ranging from 5-50 nm in size, that correlate (in terms of size) with the protein molecule employed as the imprinting template. The modified critical point drying sample preparation technique used may potentially play a key role in the imaging of all molecularly imprinted polymers, particularly those prepared in the aqueous phase

LOFAR observations of the quiet solar corona

The quiet solar corona emits meter-wave thermal bremsstrahlung. Coronal radio emission can only propagate above that radius, $R_\omega$, where the local plasma frequency eqals the observing frequency. The radio interferometer LOw Frequency ARray (LOFAR) observes in its low band (10 -- 90 MHz) solar radio emission originating from the middle and upper corona. We present the first solar aperture synthesis imaging observations in the low band of LOFAR in 12 frequencies each separated by 5 MHz. From each of these radio maps we infer $R_\omega$, and a scale height temperature, $T$. These results can be combined into coronal density and temperature profiles. We derived radial intensity profiles from the radio images. We focus on polar directions with simpler, radial magnetic field structure. Intensity profiles were modeled by ray-tracing simulations, following wave paths through the refractive solar corona, and including free-free emission and absorption. We fitted model profiles to observations with $R_\omega$ and $T$ as fitting parameters. In the low corona, $R_\omega < 1.5$ solar radii, we find high scale height temperatures up to 2.2e6 K, much more than the brightness temperatures usually found there. But if all $R_\omega$ values are combined into a density profile, this profile can be fitted by a hydrostatic model with the same temperature, thereby confirming this with two independent methods. The density profile deviates from the hydrostatic model above 1.5 solar radii, indicating the transition into the solar wind. These results demonstrate what information can be gleaned from solar low-frequency radio images. The scale height temperatures we find are not only higher than brightness temperatures, but also than temperatures derived from coronograph or EUV data. Future observations will provide continuous frequency coverage, eliminating the need for local hydrostatic density models

LOFAR tied-array imaging and spectroscopy of solar S bursts

Context. The Sun is an active source of radio emission that is often associated with energetic phenomena ranging from nanoflares to coronal mass ejections (CMEs). At low radio frequencies (&lt;100 MHz), numerous millisecond duration radio bursts have been reported, such as radio spikes or solar S bursts (where S stands for short). To date, these have neither been studied extensively nor imaged because of the instrumental limitations of previous radio telescopes. Aims. Here, LOw Frequency ARray (LOFAR) observations were used to study the spectral and spatial characteristics of a multitude of S bursts, as well as their origin and possible emission mechanisms. Methods. We used 170 simultaneous tied-array beams for spectroscopy and imaging of S bursts. Since S bursts have short timescales and fine frequency structures, high cadence (~50 ms) tied-array images were used instead of standard interferometric imaging, that is currently limited to one image per second. Results. On 9 July 2013, over 3000 S bursts were observed over a time period of ~8 h. S bursts were found to appear as groups of short-lived (&lt;1 s) and narrow-bandwidth (~2.5 MHz) features, the majority drifting at ~3.5 MHz s-1 and a wide range of circular polarisation degrees (2−8 times more polarised than the accompanying Type III bursts). Extrapolation of the photospheric magnetic field using the potential field source surface (PFSS) model suggests that S bursts are associated with a trans-equatorial loop system that connects an active region in the southern hemisphere to a bipolar region of plage in the northern hemisphere. Conclusions. We have identified polarised, short-lived solar radio bursts that have never been imaged before. They are observed at a height and frequency range where plasma emission is the dominant emission mechanism, however, they possess some of the characteristics of electron-cyclotron maser emission

SMART-1 Impact Ground-based campaign

Based on predictions of impact magnitude and cloud ejecta dynamics, we organized a SMART-1 ground-based observation campaign to perform coordinated measurements of the impact. Results from the coordinated multi-site campaign will be discussed