Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model.

Down syndrome (DS) is a genetic disorder that causes cognitive impairment. The staggering effects associated with an extra copy of human chromosome 21 (HSA21) complicates mechanistic understanding of DS pathophysiology. We examined the neuron-astrocyte interplay in a fully recapitulated HSA21 trisomy cellular model differentiated from DS-patient-derived induced pluripotent stem cells (iPSCs). By combining calcium imaging with genetic approaches, we discovered the functional defects of DS astroglia and their effects on neuronal excitability. Compared with control isogenic astroglia, DS astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. Furthermore, suppressed neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated signaling or genetically by knockdown of inositol triphosphate (IP3) receptors or S100B, a calcium binding protein coded on HSA21. Our results suggest a mechanism by which DS alters the function of astrocytes, which subsequently disturbs neuronal excitability

Single leg drop jump is affected by physical capacities in male soccer players following ACL reconstruction

Single leg drop jump (SLDJ) assessment is commonly used during the later stages of rehabilitation to identify residual deficits in reactive strength but the effects of physical capacity on kinetic and kinematic variables in male soccer players following ACL reconstruction remain unknown. Isokinetic knee extension strength, kinematics from an inertial measurement unit 3D system and SLDJ performance variables and mechanics derived from a force plate were measured in 64 professional soccer players (24.7 ± 3.4 years) prior to return to sport (RTS). SLDJ between-limb differences was measured (part 1) and players were divided into tertiles based on isokinetic knee extension strength (weak, moderate and strong) and reactive strength index (RSI) (low, medium and high) (part 2). Moderate to large significant differences between the ACL reconstructed and uninjured limb in SLDJ performance (d = 0.92–1.05), kinetic (d = 0.62–0.71) and kinematic variables (d = 0.56) were evident. Stronger athletes jumped higher (p = 0.002; d = 0.85), produced greater concentric (p = 0.001; d = 0.85) and eccentric power (p = 0.002; d = 0.84). Similar findings were present for RSI, but the effects were larger (d = 1.52–3.84). Weaker players, and in particular those who had lower RSI, displayed landing mechanics indicative of a ‘stiff’ knee movement strategy. SLDJ performance, kinetic and kinematic differences were identified between-limbs in soccer players at the end of their rehabilitation following ACL reconstruction. Players with lower knee extension strength and RSI displayed reduced performance and kinetic strategies associated with increased injury risk

Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome : a systematic review and subset meta-analysis

Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.Peer reviewedPublisher PD

BLAST+: architecture and applications

BACKGROUND: Sequence similarity searching is a very important bioinformatics task. While Basic Local Alignment Search Tool (BLAST) outperforms exact methods through its use of heuristics, the speed of the current BLAST software is suboptimal for very long queries or database sequences. There are also some shortcomings in the user-interface of the current command-line applications. RESULTS: We describe features and improvements of rewritten BLAST software and introduce new command-line applications. Long query sequences are broken into chunks for processing, in some cases leading to dramatically shorter run times. For long database sequences, it is possible to retrieve only the relevant parts of the sequence, reducing CPU time and memory usage for searches of short queries against databases of contigs or chromosomes. The program can now retrieve masking information for database sequences from the BLAST databases. A new modular software library can now access subject sequence data from arbitrary data sources. We introduce several new features, including strategy files that allow a user to save and reuse their favorite set of options. The strategy files can be uploaded to and downloaded from the NCBI BLAST web site. CONCLUSION: The new BLAST command-line applications, compared to the current BLAST tools, demonstrate substantial speed improvements for long queries as well as chromosome length database sequences. We have also improved the user interface of the command-line applications

Observations of Arp 220 using Herschel-SPIRE: An Unprecedented View of the Molecular Gas in an Extreme Star Formation Environment

We present Herschel SPIRE-FTS observations of Arp~220, a nearby ULIRG. The FTS continuously covers 190 -- 670 microns, providing a good measurement of the continuum and detection of several molecular and atomic species. We detect luminous CO (J = 4-3 to 13-12) and water ladders with comparable total luminosity; very high-J HCN absorption; OH+, H2O+, and HF in absorption; and CI and NII. Modeling of the continuum yields warm dust, with T = 66 K, and an unusually large optical depth of ~5 at 100 microns. Non-LTE modeling of the CO shows two temperature components: cold molecular gas at T ~ 50 K and warm molecular gas at T ~1350 K. The mass of the warm gas is 10% of the cold gas, but dominates the luminosity of the CO ladder. The temperature of the warm gas is in excellent agreement with H2 rotational lines. At 1350 K, H2 dominates the cooling (~20 L_sun/M_sun) in the ISM compared to CO (~0.4 L_sun/M_sun). We found that only a non-ionizing source such as the mechanical energy from supernovae and stellar winds can excite the warm gas and satisfy the energy budget of ~20 L_sun/M_sun. We detect a massive molecular outflow in Arp 220 from the analysis of strong P-Cygni line profiles observed in OH+, H2O+, and H2O. The outflow has a mass > 10^{7} M_sun and is bound to the nuclei with velocity < 250 km/s. The large column densities observed for these molecular ions strongly favor the existence of an X-ray luminous AGN (10^{44} ergs/s) in Arp 220.Comment: Accepted in ApJ on September 1, 201

Psychometric validation of the needs assessment tool : progressive disease in interstitial lung disease

ABSTRACT The inter-rater/test–retest reliability and construct validity of a palliative care needs assessment tool in interstitial lung disease (NAT:PD-ILD) were tested using NAT:PDILD- guided video-recorded consultations, and NAT:PD-ILD-guided consultations, and patient and carer-report outcomes (St George’s Respiratory Questionnaire (SGRQ)-ILD, Carer Strain Index (CSI)/Carer Support Needs Assessment Tool (CSNAT)). 11/16 items reached at least fair inter-rater agreement; 5 items reached at least moderate test–retest agreement. 4/6 patient constructs demonstrated agreement with SGRQ-I scores (Kendall’s tau-b, 0.24–20.36; P<0.05). 4/7 carer constructs agreed with the CSI/CSNAT items (kappa, 0.23–20.53). The NAT:PD-ILD is reliable and valid. Clinical effectiveness and implementation are to be evaluated

Development of structural correlations and synchronization from adaptive rewiring in networks of Kuramoto oscillators

L.P. acknowledges support from the National Science Foundation Graduate Research Fellowship Program. J.K. acknowledges support from the National Science Foundation Graduate Research Fellowship Program and NIH T32-EB020087, PD: Felix W. Wehrli. D.S.B. also acknowledges support from the John D. and Catherine T. MacArthur Foundation, the Alfred P. Sloan Foundation, and the National Science Foundation (BCS-1441502, CAREER PHY-1554488, BCS-1631550, and CNS-1626008). We also thank two anonymous reviewers whose comments greatly improved the quality of this work. The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding agencies.Peer reviewedPublisher PD

Theory and Applications of Non-Relativistic and Relativistic Turbulent Reconnection

Realistic astrophysical environments are turbulent due to the extremely high Reynolds numbers. Therefore, the theories of reconnection intended for describing astrophysical reconnection should not ignore the effects of turbulence on magnetic reconnection. Turbulence is known to change the nature of many physical processes dramatically and in this review we claim that magnetic reconnection is not an exception. We stress that not only astrophysical turbulence is ubiquitous, but also magnetic reconnection itself induces turbulence. Thus turbulence must be accounted for in any realistic astrophysical reconnection setup. We argue that due to the similarities of MHD turbulence in relativistic and non-relativistic cases the theory of magnetic reconnection developed for the non-relativistic case can be extended to the relativistic case and we provide numerical simulations that support this conjecture. We also provide quantitative comparisons of the theoretical predictions and results of numerical experiments, including the situations when turbulent reconnection is self-driven, i.e. the turbulence in the system is generated by the reconnection process itself. We show how turbulent reconnection entails the violation of magnetic flux freezing, the conclusion that has really far reaching consequences for many realistically turbulent astrophysical environments. In addition, we consider observational testing of turbulent reconnection as well as numerous implications of the theory. The former includes the Sun and solar wind reconnection, while the latter include the process of reconnection diffusion induced by turbulent reconnection, the acceleration of energetic particles, bursts of turbulent reconnection related to black hole sources as well as gamma ray bursts. Finally, we explain why turbulent reconnection cannot be explained by turbulent resistivity or derived through the mean field approach.Comment: 66 pages, 24 figures, a chapter of the book "Magnetic Reconnection - Concepts and Applications", editors W. Gonzalez, E. N. Parke

Quinta-Gamelin Community Center: Architectural Design

The new facility will add meeting space for many of community organizations and sport leagues as well as people interested in renting the gymnasium and meeting rooms. Last year our community center gymnasium was given out 192 times on an average of two hours each, our meeting room was given out 68 times. Similar towns rent these facilities at approximately $15.00 an hour