Rock drumming enhances motor and psychosocial skills of children with emotional and behavioral difficulties

Drumming may have therapeutic and learning benefits but there exists little causal evidence regarding the benefits for children with emotional and behavioural difficulties (EBD) such as Autistic Spectrum Disorder. Six EBD pupils (EBD Drum) and 6 peers (Peer Drum) were given 2, 30 minute rock drumming lessons per week, over 5 weeks. Six matched individuals received no drumming instruction (3=EBD Control; 3=Peer Control). An exploratory, mixed-methods analysis was used to explore quantitative changes in skills and qualitative perspectives of the teaching staff. All pupils were tested two times (pretest and posttest) on drumming ability and Motor skills (Movement Assessment Battery for Children, version 2). Teacher’s rating of social behaviour (Strength and Difficulties Questionnaire; SDQ) was tested two times (pretest and retention).Significant differences in total SDQ difficulties between the four groups (χ2(3) = 8.210, p = 0.042) and the hyperactivity subscale (χ2(3) = 10.641, p = 0.014) were observed. The EBD Drum group had greater reductions in total difficulties compared to the Peer Drum (p = 0.009) group and specifically greater reductions in hyperactivity compared to Peer Drum (p = 0.046) and the EBD Control (p = 0.006) group. In follow-up interviews, staff spoke positively about changes in pupil’s attitudes towards learning and social confidence. The positive changes to social and behavioural skills reported in this pilot study are similar to those recorded for other music modalities

An analog of glibenclamide selectively enhances autophagic degradation of misfolded α1-antitrypsin Z

The classical form of α1-antitrypsin deficiency (ATD) is characterized by intracellular accumulation of the misfolded variant α1-antitrypsin Z (ATZ) and severe liver disease in some of the affected individuals. In this study, we investigated the possibility of discovering novel therapeutic agents that would reduce ATZ accumulation by interrogating a C. elegans model of ATD with high-content genome-wide RNAi screening and computational systems pharmacology strategies. The RNAi screening was utilized to identify genes that modify the intracellular accumulation of ATZ and a novel computational pipeline was developed to make high confidence predictions on repurposable drugs. This approach identified glibenclamide (GLB), a sulfonylurea drug that has been used broadly in clinical medicine as an oral hypoglycemic agent. Here we show that GLB promotes autophagic degradation of misfolded ATZ in mammalian cell line models of ATD. Furthermore, an analog of GLB reduces hepatic ATZ accumulation and hepatic fibrosis in a mouse model in vivo without affecting blood glucose or insulin levels. These results provide support for a drug discovery strategy using simple organisms as human disease models combined with genetic and computational screening methods. They also show that GLB and/or at least one of its analogs can be immediately tested to arrest the progression of human ATD liver disease.</div

Multiple-University Extension Program Addresses Postdisaster Oil Spill Needs Through Private Funding Partnership

In response to the Deepwater Horizon Oil Spill, the Gulf of Mexico Research Initiative (GoMRI) was formed to answer oil spill–related scientific questions. However, peer-reviewed scientific discoveries were not reaching people whose livelihoods depended on a healthy Gulf of Mexico. GoMRI and the four Gulf of Mexico Sea Grant programs partnered to develop a regional Extension program with a team of multidisciplinary specialists and a regional manager embedded within the Sea Grant programs. The team answered oil spill science questions from target audiences. The program leaders also identified the value of adding a regional Extension communicator to enhance their Extension products

Templates for Convex Cone Problems with Applications to Sparse Signal Recovery

This paper develops a general framework for solving a variety of convex cone problems that frequently arise in signal processing, machine learning, statistics, and other fields. The approach works as follows: first, determine a conic formulation of the problem; second, determine its dual; third, apply smoothing; and fourth, solve using an optimal first-order method. A merit of this approach is its flexibility: for example, all compressed sensing problems can be solved via this approach. These include models with objective functionals such as the total-variation norm, ||Wx||_1 where W is arbitrary, or a combination thereof. In addition, the paper also introduces a number of technical contributions such as a novel continuation scheme, a novel approach for controlling the step size, and some new results showing that the smooth and unsmoothed problems are sometimes formally equivalent. Combined with our framework, these lead to novel, stable and computationally efficient algorithms. For instance, our general implementation is competitive with state-of-the-art methods for solving intensively studied problems such as the LASSO. Further, numerical experiments show that one can solve the Dantzig selector problem, for which no efficient large-scale solvers exist, in a few hundred iterations. Finally, the paper is accompanied with a software release. This software is not a single, monolithic solver; rather, it is a suite of programs and routines designed to serve as building blocks for constructing complete algorithms.Comment: The TFOCS software is available at http://tfocs.stanford.edu This version has updated reference

Myofunctional and Dentofacial Relationships in Second Grade Children.

One hundred and thirty-three second graders in rural public school were assessed on a number of dental, skeletal, and oral muscle function measures. Correlational analyses were conducted in order to determine whether specific myofunctional variables were associated with dentofacial development. Significant relationships were observed between open mouth posture and a narrow maxillary arch and long facial height. Labial and lingual rest and swallow patterns were also related to poor coordination of lip and tongue movements

Gender Specific Re-organization of Resting-State Networks in Older Age

Advancing age is commonly associated with changes in both brain structure and function. Recently, the suggestion that alterations in brain connectivity may drive disruption in cognitive abilities with age has been investigated. However, the interaction between the effects of age and gender on the reorganisation of resting-state networks is not fully understood. This study sought to investigate the effect of both age and gender on intra- and inter-network functional connectivity (FC) and the extent to which RSN node definition may alter with older age. We obtained resting-state functional magnetic resonance images from younger (n=20) and older (n=20) adults and assessed the FC of three main cortical networks: default mode (DMN), dorsal attention (DAN) and saliency (SN). Older adults exhibited reduced DMN intra-network FC and increased inter-network FC between the anterior cingulate cortex (ACC) and nodes of the DAN, in comparison to younger participants. Furthermore, this increase in ACC-DAN inter-network FC with age was driven largely by male participants. However, further analyses suggested that the spatial location of ACC, bilateral anterior insula and orbitofrontal cortex RSN nodes changed with older age and that age-related gender differences in FC may reflect spatial re-organisation rather than increases or decreases in FC strength alone. These differences in both the FC and spatial distribution of RSNs between younger and older adults provide evidence of reorganisation of fundamental brain networks with age, which is modulated by gender. These results highlight the need to further investigate changes in both intra- and inter- network FC with age, whilst also exploring the modifying effect of gender. They also emphasise the difficulties in directly comparing the FC of RSN nodes between groups and suggest that caution should be taken when using the same RSN node definitions for different age or patient groups to investigate FC

Solution structure of the SGTA dimerisation domain and investigation of its interactions with the ubiquitin-like domains of BAG6 and UBL4A

BACKGROUND: The BAG6 complex resides in the cytosol and acts as a sorting point to target diverse hydrophobic protein substrates along their appropriate paths, including proteasomal degradation and ER membrane insertion. Composed of a trimeric complex of BAG6, TRC35 and UBL4A, the BAG6 complex is closely associated with SGTA, a co-chaperone from which it can obtain hydrophobic substrates. METHODOLOGY AND PRINCIPAL FINDINGS: SGTA consists of an N-terminal dimerisation domain (SGTA_NT), a central tetratricopeptide repeat (TPR) domain, and a glutamine rich region towards the C-terminus. Here we solve a solution structure of the SGTA dimerisation domain and use biophysical techniques to investigate its interaction with two different UBL domains from the BAG6 complex. The SGTA_NT structure is a dimer with a tight hydrophobic interface connecting two sets of four alpha helices. Using a combination of NMR chemical shift perturbation, isothermal titration calorimetry (ITC) and microscale thermophoresis (MST) experiments we have biochemically characterised the interactions of SGTA with components of the BAG6 complex, the ubiquitin-like domain (UBL) containing proteins UBL4A and BAG6. We demonstrate that the UBL domains from UBL4A and BAG6 directly compete for binding to SGTA at the same site. Using a combination of structural and interaction data we have implemented the HADDOCK protein-protein interaction docking tool to generate models of the SGTA-UBL complexes. SIGNIFICANCE: This atomic level information contributes to our understanding of the way in which hydrophobic proteins have their fate decided by the collaboration between SGTA and the BAG6 complex

The National Childrens Study: Recruitment Outcomes Using the Provider-Based Recruitment Approach

In 2009, the National Children’s Study (NCS) Vanguard Study tested the feasibility of household-based recruitment and participant enrollment using a birth-rate probability sample. In 2010, the NCS Program Office launched 3 additional recruitment approaches. We tested whether provider-based recruitment could improve recruitment outcomes compared with household-based recruitment

Examining the stability of membrane proteins within SMALPs

Amphipathic co-polymers such as styrene-maleic acid (SMA) have gained popularity over the last few years due to their ability and ease of use in solubilising and purifying membrane proteins in comparison to conventional methods of extraction such as detergents. SMA2000 is widely used for membrane protein studies and is considered as the optimal polymer for this technique. In this study a side-by-side comparison of SMA2000 with the polymer SZ30010 was carried out as both these polymers have similar styrene:maleic acid ratios and average molecular weights. Ability to solubilise, purify and stabilise membrane proteins was tested using three structurally different membrane proteins. Our results show that both polymers can be used to extract membrane proteins at a comparable efficiency to conventional detergent dodecylmaltoside (DDM). SZ30010 was found to give a similar protein yield and, SMALP disc size as SMA2000, and both polymers offered an increased purity and increased thermostability compared to DDM. Further investigation was conducted to investigate SMALP sensitivity to divalent cations. It was found that the sensitivity is polymer specific and not dependent on the protein encapsulated. Neither is it affected by the concentration of SMALPs. Larger divalent cations such as Co2+ and Zn2+ resulted in an increased sensitivity

Status of the PALM-3000 high-order adaptive optics system

The PALM-3000 upgrade to the Palomar Adaptive Optics system on the 5.1 meter Hale telescope will deliver extreme adaptive optics correction in near-infrared wavelengths and diffraction-limited images in visible wavelengths. PALM-3000 will use a 3388-actuator tweeter and a 241-actuator woofer deformable mirror, a Shack-Hartmann wavefront sensor with selectable pupil sampling, and an innovative wavefront control computer based on a cluster of 17 graphics processing units to correct wavefront aberrations at scales as fine as 8.1 cm at the telescope pupil using natural guide stars. The system is currently undergoing integration and testing, with deployment at Palomar Observatory planned in early 2011. We present the detailed design of key aspects of the adaptive optics system, and the current status of the deformable mirror characterization, wavefront sensor performance, and testbed activities