A non-apoptotic role for caspase-9 in muscle differentiation

Caspases, a family of cysteine proteases most often investigated for their roles in apoptosis, have also been demonstrated to have functions that are vital for the efficient execution of cell differentiation. One such role that has been described is the requirement of caspase-3 for the differentiation of skeletal myoblasts into myotubes but, as yet, the mechanism leading to caspase-3 activation in this case remains elusive. Here, we demonstrate that caspase-9, an initiator caspase in the mitochondrial death pathway, is responsible for the activation of caspase-3 in differentiating C2C12 cells. Reduction of caspase-9 levels, using an shRNA construct, prevented caspase-3 activation and inhibited myoblast fusion. Myosin-heavy-chain expression, which accompanies myoblastic differentiation, was not caspase-dependent. Overexpression of Bcl-xL, a protein that inhibits caspase-9 activation, had the same effect on muscle differentiation as knockdown of caspase-9. These data suggest that the mitochondrial pathway is required for differentiation; however, the release of cytochrome c or Smac (Diablo) could not be detected, raising the possibility of a novel mechanism of caspase-9 activation during muscle differentiation.</jats:p

Sequence and Chemostratigraphy of the Middle Cambrian Succession in Nevada and Utah

The House Range Embayment of western Utah and eastern Nevada was a prominent topographic feature on the passive margin of western North America during the middle and late Cambrian. In this study, detailed documentation of sequence boundaries, and their intervening sequences across a platform-to-basin transect of the House Range Embayment was used to establish a sequence-stratigraphic framework from which the depositional history of the embayment was deciphered. This framework was then used to test the hypothesis that the House Range Embayment formed by tectonic subsidence. In addition, the chemostratigraphic (δ13Ccarb) record across the embayment was analyzed within this framework to (1) document the relationship between the FAD of P. atavus and the negative δ13C Drumian Carbon Isotope Excursion (DICE), (2) clarify the relationship between sea-level change and the DICE, (3) refine the definition of the DICE event in a sequence stratigraphic framework, (4) test the hypothesis that the embayment was a restricted anoxic basin, and (5) explore the possibility of using carbon isotope excursions for regional/global stratigraphic correlation. Five sequence boundaries were identified in the platform and correlated with condensed intervals in the basin within the known biostratigraphic framework. These sequence boundaries document the initial tectonic formation of the embayment and its subsequent infilling during tectonic quiescence. Five carbon isotope profiles indicate that the DICE is located stratigraphically above the FAD of Ptychagnostus atavus in the embayment, associated with transgressive deposits on the southern platform, and with stratigraphic condensation in the basin. Two longer carbon isotope profiles do not reveal significant isotopic variability that can be attributed solely to local carbon cycling in an anoxic basin but they do reveal the effect of diagenetic alteration of platform values. The results also indicate that chemostratigraphic correlation in poorly dated successions deposited from significantly different paleoenvironments should be approached with caution

An investigation of the neurocognitive phenotype of 22Q11.2 deletion syndrome across developmental stages.

Background: 22q11.2 deletion syndrome (22qDS) is a common microdeletion disorder arising from a deletion on the long (q) arm of chromosome 22. It is associated with a complex and variably expressed phenotype, which includes a range of neuroanatomical and cognitive abnormalities. The effect of general intellectual disability on the neurocognitive profile of 22qDS and the development of cognitive abilities across developmental stages requires further research. Aims: The current study aims to investigate the extent to which the neurocognitive profile of 22qDS is mediated by general intellectual impairment and to construct cross-sectional developmental trajectories of executive functions and memory abilities in children, adolescents and adults with 22qDS. Methods: Standardised cognitive test batteries were employed to assess the key areas of visual-motor function, executive function and memory in children, adolescents and adults with 22qDS. The effects of IQ were assessed using an IQ-matched control group and a statistical method for testing for differential deficits in cognitive functioning. Cross-sectional developmental trajectories were constructed to examine changes in cognitive profiles across age ranges. Results: Each age group displayed cognitive profiles characterised by preserved verbal/auditory processing and selective deficits in visual and spatial perception. Compared to IQ-matched controls, the child/adolescent group exhibited differential deficits in fine motor speed and visuospatial memory but they did not differ from IQ-matched controls on any measure of executive function. The adult group did not display any cognitive deficit in excess of their overall intellectual impairment. Visuospatial and pattern recognition memory were observed to improve significantly across the age range. Executive functions, with the exception of verbal working memory, displayed no significant improvement across the age range. Conclusions: These findings suggest that the impact of general intellectual disability on the neurocognitive phenotype of 22qDS was mediated by the developmental stage of the study participants. Fine motor ability and visuospatial recall may exhibit developmental delay relative to other cognitive abilities and pre-frontally mediated executive functions appear to exhibit atypical developmental trajectories

The SPLASH Survey: Kinematics of Andromeda's Inner Spheroid

The combination of large size, high stellar density, high metallicity, and Sersic surface brightness profile of the spheroidal component of the Andromeda galaxy (M31) within R_proj ~ 20 kpc suggest that it is unlike any subcomponent of the Milky Way. In this work we capitalize on our proximity to and external view of M31 to probe the kinematical properties of this "inner spheroid." We employ a Markov chain Monte Carlo (MCMC) analysis of resolved stellar kinematics from Keck/DEIMOS spectra of 5651 red giant branch stars to disentangle M31's inner spheroid from its stellar disk. We measure the mean velocity and dispersion of the spheroid in each of five spatial bins after accounting for a locally cold stellar disk as well as the Giant Southern Stream and associated tidal debris. For the first time, we detect significant spheroid rotation (v_rot ~ 50 km/s) beyond R_proj ~ 5 kpc. The velocity dispersion decreases from about 140 km/s at R_proj = 7 kpc to 120 km/s at R_proj = 14 kpc, consistent to 2 sigma with existing measurements and models. We calculate the probability that a given star is a member of the spheroid and find that the spheroid has a significant presence throughout the spatial extent of our sample. Lastly, we show that the flattening of the spheroid is due to velocity anisotropy in addition to rotation. Though this suggests that the inner spheroid of M31 more closely resembles an elliptical galaxy than a typical spiral galaxy bulge, it should be cautioned that our measurements are much farther out (2 - 14 r_eff) than for the comparison samples.Comment: Accepted for publication in Ap

Attention deficit hyperactivity disorder: an exploratory analysis of treatment utilization

Attention Deficit Hyperactivity Disorder is a chronic and pervasive disorder. Medication as well as psychosocial treatment has proven effective in managing the symptoms of ADHD in children. Research has found that the symptoms of hyperactivity and impulsivity decrease with age while the symptoms of inattention stay stable over time. The current analysis will consider whether treatment for ADHD is concurrent with this trend in symptom presentation as well as whether gender plays a role in treatment utilization. It is hypothesized that children diagnosed with ADHD combined type will receive more treatment with medication than psychosocial treatment and treatment overall will decrease with age in accordance with the waning of hyperactive symptoms. It is also hypothesized that children diagnosed with ADHD inattentive type will receive more psychosocial treatment than treatment with medication, as their symptoms are not as externalizing and disruptive. However, the use of treatment (medication and psychosocial) will increase with age as the symptoms of Inattention become more apparent. The analysis will also consider differences in medication use in terms of gender.M.S., Psychology -- Drexel University, 200

Coast-to-Interior Gradient in Recent Northwest Greenland Precipitation Trends (1952–2012)

The spatial and temporal variability of precipitation on the Greenland ice sheet is an essential component of surface mass balance, which has been declining in recent years with rising temperatures. We present an analysis of precipitation trends in northwest (NW) Greenland (1952–2012) using instrumental (coastal meteorological station) and proxy records (snow pits and ice cores) to characterize the precipitation gradient from the coast to the ice sheet interior. Snow-pit-derived precipitation near the coast (1950–2000) has increased (~7% decade−1, p \u3c 0.01) whereas there is no significant change observed in interior snow pits. This trend holds for 1981–2012, where calculated precipitation changes decrease in magnitude with increasing distance from the coast: 13% decade−1 (2.4 mm water equivalent (w.e.) decade−2) at coastal Thule air base (AB), 8.6% decade−1 (4.7 mm w.e. decade−2) at the 2Barrel ice core site 150 km from Thule AB, −5.2% decade−1 (1.7 mm w.e. decade−2) at Camp Century located 205 km from Thule AB, and 4.4% decade−1 (1.0 mm w.e. decade−2) at B26 located 500 km from Thule AB. In general, annually averaged precipitation and annually and seasonally averaged mean air temperatures observed at Thule AB follow trends observed in composite coastal Greenland time series, with both notably indicating winter as the fastest warming season in recent periods (1981–2012). Trends (1961–2012) in seasonal precipitation differ, specifically with NW Greenland summer precipitation increasing (~0.6 mm w.e. decade−2) in contrast with decreasing summer precipitation in the coastal composite time series (3.8 mm w.e. decade−2). Differences in precipitation trends between NW Greenland and coastal composite Greenland underscore the heterogeneity in climate influences affecting precipitation. In particular, recent (1981–2012) changes in NW Greenland annual precipitation are likely a response to a weakening North Atlantic oscillation

Accelerated Particle Swarm Optimization and Support Vector Machine for Business Optimization and Applications

Business optimization is becoming increasingly important because all business activities aim to maximize the profit and performance of products and services, under limited resources and appropriate constraints. Recent developments in support vector machine and metaheuristics show many advantages of these techniques. In particular, particle swarm optimization is now widely used in solving tough optimization problems. In this paper, we use a combination of a recently developed Accelerated PSO and a nonlinear support vector machine to form a framework for solving business optimization problems. We first apply the proposed APSO-SVM to production optimization, and then use it for income prediction and project scheduling. We also carry out some parametric studies and discuss the advantages of the proposed metaheuristic SVM.Comment: 12 page

Phosphinecarboxamide based InZnP QDs – an air tolerant route to luminescent III–V semiconductors

We describe a new synthetic methodology for the preparation of high quality, emission tuneable InP-based quantum dots (QDs) using a solid, air- and moisture-tolerant primary phosphine as a group-V precursor. This presents a significantly simpler synthetic pathway compared to the state-of-the-art precursors currently employed in phosphide quantum dot synthesis which are volatile, dangerous and air-sensitive, e.g. P(Si(CH3)3)3

Human Papillomavirus E6 Triggers Upregulation of the Antiviral and Cancer Genomic DNA Deaminase APOBEC3B

ABSTRACT Several recent studies have converged upon the innate immune DNA cytosine deaminase APOBEC3B (A3B) as a significant source of genomic uracil lesions and mutagenesis in multiple human cancers, including those of the breast, head/neck, cervix, bladder, lung, ovary, and other tissues. A3B is upregulated in these tumor types relative to normal tissues, but the mechanism is unclear. Because A3B also has antiviral activity in multiple systems and is a member of the broader innate immune response, we tested the hypothesis that human papillomavirus (HPV) infection causes A3B upregulation. We found that A3B mRNA expression and enzymatic activity were upregulated following transfection of a high-risk HPV genome and that this effect was abrogated by inactivation of E6. Transduction experiments showed that the E6 oncoprotein alone was sufficient to cause A3B upregulation, and a panel of high-risk E6 proteins triggered higher A3B levels than did a panel of low-risk or noncancer E6 proteins. Knockdown experiments in HPV-positive cell lines showed that endogenous E6 is required for A3B upregulation. Analyses of publicly available head/neck cancer data further support this relationship, as A3B levels are higher in HPV-positive cancers than in HPV-negative cancers. Taken together with the established role for high-risk E6 in functional inactivation of TP53 and published positive correlations in breast cancer between A3B upregulation and genetic inactivation of TP53, our studies suggest a model in which high-risk HPV E6, possibly through functional inactivation of TP53, causes derepression of A3B gene transcription. This would lead to a mutator phenotype that explains the observed cytosine mutation biases in HPV-positive head/neck and cervical cancers

The young stellar population at the center of NGC 205

Context. NGC 205 is a peculiar dwarf elliptical galaxy hosting in its center a population of young blue stars. Their origin is still matter of debate, the central fresh star formation activity possibly being related to dynamical interactions between NGC 205 and M31. Aims. The star formation history in the central 30\arcsec ($\sim$120 pc) around the NGC 205 central nucleus is investigated in order to obtain clues to the origin of the young stellar population. Methods. Deep HST/ACS CCD photometry is compared with theoretical isochrones and luminosity functions to characterize the stellar content of the region under study and compute the recent SF rate. Results. Our photometry reveals a previously undetected blue plume of young stars clearly distinguishable down to I$\simeq$26. Our analysis suggests that 1.9$\times10^5$ M$_\odot$ were produced between approximately 62 Myr and 335 Myr ago in the NGC 205 inner regions, with a latest minor episode occurring $\sim$25 Myr ago. This implies a star formation rate of $\sim7\times10^{-4}$ M$_\odot$/yr over this period. Conclusions. The excellent fit of the observed luminosity function of young main sequence stars obtained with a model having a constant star formation rate argues against a tidally triggered star formation activity over the last $\sim$300 Myr. Rather, a constant SF may be consistent with NGC 205 being on its first interaction with M 31.Comment: 5 pages, 2 figures, accepted for publication in A&A letter