Neurocognitive Predictors of Treatment Response to Randomized Treatment in Adults with Tic Disorders

Tourette\u27s disorder (TS) and chronic tic disorder (CTD) are neurodevelopmental disorders characterized by involuntary vocal and motor tics. Consequently, TS/CTD have been conceptualized as disorders of cognitive and motor inhibitory control. However, most neurocognitive studies have found comparable or superior inhibitory capacity among individuals with TS/CTD relative to healthy controls. These findings have led to the hypothesis that individuals with TS/CTD develop increased inhibitory control due to the constant need to inhibit tics. However, the role of cognitive control in TS/CTD is not yet understood, particularly in adults. To examine the role of inhibitory control in TS/CTD, the present study investigated this association by assessing the relationship between inhibitory control and treatment response in a large sample of adults with TS/CTD. As part of a large randomized trial comparing behavior therapy versus supportive psychotherapy for TS/CTD, a battery of tests, including tests of inhibitory control was administered to 122 adults with TS/CTD at baseline. We assessed the association between neuropsychological test performance and change in symptom severity, as well as compared the performance of treatment responders and non-responders as defined by the Clinical Global Impression Scale. Results indicated that change in symptoms, and treatment response were not associated with neuropsychological performance on tests of inhibitory control, intellectual ability, or motor function, regardless of type of treatment. The finding that significant change in symptom severity of TS/CTD patients is not associated with impairment or change in inhibitory control regardless of treatment type suggests that inhibitory control may not be a clinically relevant facet of these disorders in adults

Strong Gravitational Lensing by Sgr A*

In recent years, there has been increasing recognition of the potential of the galactic center as a probe of general relativity in the strong field. There is almost certainly a black hole at Sgr A* in the galactic center, and this would allow us the opportunity to probe dynamics near the exterior of the black hole. In the last decade, there has been research into extreme gravitational lensing in the galactic center. Unlike in most applications of gravitational lensing, where the bending angle is of the order of several arc seconds, very large bending angles are possible for light that closely approaches a black hole. Photons may even loop multiple times around a black hole before reaching the observer. There have been many proposals to use light's close approach to the black hole as a probe of the black hole metric. Of particular interest is the property of light lensed by the S stars orbiting in the galactic center. This paper will review some of the attempts made to study extreme lensing as well as extend the analysis of lensing by S stars. In particular, we are interested in the effect of a Reissner-Nordstrom like 1/r^2 term in the metric and how this would affect the properties of relativistic images.Comment: 13 pages, 9 figures. Submitted as invited review article for the GR19 issue of CQ

Synchronization of an optomechanical system to an external drive

Optomechanical systems driven by an effective blue-detuned laser can exhibit self-sustained oscillations of the mechanical oscillator. These self-oscillations are a prerequisite for the observation of synchronization. Here, we study the synchronization of the mechanical oscillations to an external reference drive. We study two cases of reference drives: (1) an additional laser applied to the optical cavity; (2) a mechanical drive applied directly to the mechanical oscillator. Starting from a master equation description, we derive a microscopic Adler equation for both cases, valid in the classical regime in which the quantum shot noise of the mechanical self-oscillator does not play a role. Furthermore, we numerically show that, in both cases, synchronization arises also in the quantum regime. The optomechanical system is therefore a good candidate for the study of quantum synchronization.This work was financially supported by the Swiss SNF and the NCCR Quantum Science and Technology. A.N. holds a University Research Fellowship from the Royal Society and acknowledges support from the Winton Programme for the Physics of Sustainabilit

Toward a Framework for Systematic Error Modeling of NASA Spaceborne Radar with NOAA/NSSL Ground Radar-Based National Mosaic QPE

Characterization of the error associated to satellite rainfall estimates is a necessary component of deterministic and probabilistic frameworks involving space-born passive and active microwave measurement") for applications ranging from water budget studies to forecasting natural hazards related to extreme rainfall events. We focus here on the error structure of NASA's Tropical Rainfall Measurement Mission (TRMM) Precipitation Radar (PR) quantitative precipitation estimation (QPE) at ground. The problem is addressed by comparison of PR QPEs with reference values derived from ground-based measurements using NOAA/NSSL ground radar-based National Mosaic and QPE system (NMQ/Q2). A preliminary investigation of this subject has been carried out at the PR estimation scale (instantaneous and 5 km) using a three-month data sample in the southern part of US. The primary contribution of this study is the presentation of the detailed steps required to derive trustworthy reference rainfall dataset from Q2 at the PR pixel resolution. It relics on a bias correction and a radar quality index, both of which provide a basis to filter out the less trustworthy Q2 values. Several aspects of PR errors arc revealed and quantified including sensitivity to the processing steps with the reference rainfall, comparisons of rainfall detectability and rainfall rate distributions, spatial representativeness of error, and separation of systematic biases and random errors. The methodology and framework developed herein applies more generally to rainfall rate estimates from other sensors onboard low-earth orbiting satellites such as microwave imagers and dual-wavelength radars such as with the Global Precipitation Measurement (GPM) mission

microRNA-184 induces a commitment switch to epidermal differentiation

miR-184 is a highly evolutionary conserved microRNA (miRNA) from fly to human. The importance of miR-184 was underscored by the discovery that point mutations in miR-184 gene led to corneal/lens blinding disease. However, miR-184-related function in vivo remained unclear. Here, we report that the miR-184 knockout mouse model displayed increased p63 expression in line with epidermal hyperplasia, while forced expression of miR-184 by stem/progenitor cells enhanced the Notch pathway and induced epidermal hypoplasia. In line, miR-184 reduced clonogenicity and accelerated differentiation of human epidermal cells. We showed that by directly repressing cytokeratin 15 (K15) and FIH1, miR-184 induces Notch activation and epidermal differentiation. The disease-causing miR-184C57U mutant failed to repress K15 and FIH1 and to induce Notch activation, suggesting a loss-of-function mechanism. Altogether, we propose that, by targeting K15 and FIH1, miR-184 regulates the transition from proliferation to early differentiation, while mis-expression or mutation in miR-184 results in impaired homeostasis

The Effects of Dietary Linoleic Acid and Hydrophilic Antioxidants on Basal, Peak, and Sustained Metabolism in Flight‐trained European Starlings

Dietary micronutrients have the ability to strongly influence animal physiology and ecology. For songbirds, dietary polyunsaturated fatty acids (PUFAs) and antioxidants are hypothesized to be particularly important micronutrients because of their influence on an individual\u27s capacity for aerobic metabolism and recovery from extended bouts of exercise. However, the influence of specific fatty acids and hydrophilic antioxidants on whole‐animal performance remains largely untested. We used diet manipulations to directly test the effects of dietary PUFA, specifically linoleic acid (18:2n6), and anthocyanins, a hydrophilic antioxidant, on basal metabolic rate (BMR), peak metabolic rate (PMR), and rates of fat catabolism, lean catabolism, and energy expenditure during sustained flight in a wind tunnel in European starlings (Sturnus vulgaris). BMR, PMR, energy expenditure, and fat metabolism decreased and lean catabolism increased over the course of the experiment in birds fed a high (32%) 18:2n6 diet, while birds fed a low (13%) 18:2n6 diet exhibited the reverse pattern. Additionally, energy expenditure, fat catabolism, and flight duration were all subject to diet‐specific effects of whole‐body fat content. Dietary antioxidants and diet‐related differences in tissue fatty acid composition were not directly related to any measure of whole‐animal performance. Together, these results suggest that the effect of dietary 18:2n6 on performance was most likely the result of the signaling properties of 18:2n6. This implies that dietary PUFA influence the energetic capabilities of songbirds and could strongly influence songbird ecology, given their availability in terrestrial systems

A Differential Effect of E. coli Toxin-Antitoxin Systems on Cell Death in Liquid Media and Biofilm Formation

Toxin-antitoxin (TA) modules are gene pairs specifying for a toxin and its antitoxin and are found on the chromosomes of many bacteria including pathogens. Here we report how each of five such TA systems in E. coli affect bacterial cell death differently in liquid media and during biofilm formation. Of all these systems, only the TA system mazEF mediated cell death both in liquid media and during biofilm formation. At the other extreme, as our results have revealed here, the TA system dinJ-YafQ is unique in that it is involved only in the death process during biofilm formation. Cell death governed by mazEF and dinJ-YafQ seems to participate in biofilm formation through a novel mechanism

Exploiting structural and topological information to improve prediction of RNA-protein binding sites

The breast and ovarian cancer susceptibility gene BRCA1 encodes a multifunctional tumor suppressor protein BRCA1, which is involved in regulating cellular processes such as cell cycle, transcription, DNA repair, DNA damage response and chromatin remodeling. BRCA1 protein, located primarily in cell nuclei, interacts with multiple proteins and various DNA targets. It has been demonstrated that BRCA1 protein binds to damaged DNA and plays a role in the transcriptional regulation of downstream target genes. As a key protein in the repair of DNA double-strand breaks, the BRCA1-DNA binding properties, however, have not been reported in detail

Automatic prediction of catalytic residues by modeling residue structural neighborhood

Background: Prediction of catalytic residues is a major step in characterizing the function of enzymes. In its simpler formulation, the problem can be cast into a binary classification task at the residue level, by predicting whether the residue is directly involved in the catalytic process. The task is quite hard also when structural information is available, due to the rather wide range of roles a functional residue can play and to the large imbalance between the number of catalytic and non-catalytic residues.Results: We developed an effective representation of structural information by modeling spherical regions around candidate residues, and extracting statistics on the properties of their content such as physico-chemical properties, atomic density, flexibility, presence of water molecules. We trained an SVM classifier combining our features with sequence-based information and previously developed 3D features, and compared its performance with the most recent state-of-the-art approaches on different benchmark datasets. We further analyzed the discriminant power of the information provided by the presence of heterogens in the residue neighborhood.Conclusions: Our structure-based method achieves consistent improvements on all tested datasets over both sequence-based and structure-based state-of-the-art approaches. Structural neighborhood information is shown to be responsible for such results, and predicting the presence of nearby heterogens seems to be a promising direction for further improvements.Journal ArticleResearch Support, N.I.H. Extramuralinfo:eu-repo/semantics/publishe

Escherichia coli MazF Leads to the Simultaneous Selective Synthesis of Both “Death Proteins” and “Survival Proteins”

The Escherichia coli mazEF module is one of the most thoroughly studied toxin–antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. MazF is an endoribonuclease that leads to the inhibition of protein synthesis by cleaving mRNAs at ACA sequences. Here, using 2D-gels, we show that in E. coli, although MazF induction leads to the inhibition of the synthesis of most proteins, the synthesis of an exclusive group of proteins, mostly smaller than about 20 kDa, is still permitted. We identified some of those small proteins by mass spectrometry. By deleting the genes encoding those proteins from the E. coli chromosome, we showed that they were required for the death of most of the cellular population. Under the same experimental conditions, which induce mazEF-mediated cell death, other such proteins were found to be required for the survival of a small sub-population of cells. Thus, MazF appears to be a regulator that induces downstream pathways leading to death of most of the population and the continued survival of a small sub-population, which will likely become the nucleus of a new population when growth conditions become less stressful