Subunit Stoichiometry of a Heteromultimeric G protein-coupled Inward-rectifier K^+ Channel

We investigated the stoichiometry of the heteromultimeric G protein-coupled inward-recitfier K^+ channel (GIRK) formed from GIRK1 and GIRK4 subunits. Multimeric GIRK constructs with several concatenated channel subunits were expressed in Xenopus oocytes. Coexpression of various trimeric constructs with different monomers clearly showed that the functional channel has stoichiometry (GIRK1)_2(GIRK4)_2. Efforts to establish a preferred arrangement of subunits around the channel pore suggest that more than one arrangement may be viable

A Chromosomal Deletion and New Frameshift Mutation Cause ARSACS in an African-American

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a rare, progressive, neurodegenerative disease characterized by ataxia, spasticity and polyneuropathy. First described in the French-Canadian population of Quebec in 1978, ARSACS has since been identified in multiple patients worldwide. In this clinical case report, we describe the evaluation of an 11-years-old African-American male who presented to neuromuscular clinic for assessment of a gait abnormality. He had a history of gross motor delay since early childhood, frequent falls and a below average IQ. Chromosomal microarray revealed a 1.422 megabase loss in the 13q12.12 region, which includes the SACS gene. Next Generation Sequencing then showed a novel, predicted to be pathogenic missense mutation (c.11824dup) of this gene. His clinical presentation and neurological imaging further confirmed the diagnosis of ARSACS. To our knowledge, this is the first reported case of this disease in the African-American population of the United States. This case report further highlights the growing trend of identifying genetic diseases previously restricted to single, ethnically isolated regions in many different ethnic groups worldwide

Conformational effects on high-spin organic molecules

The ability of m-phenylene to ferromagnetically couple spin-containing substituents that are substantially twisted out of conjugation is investigated. The "bis(TMM)" strategy is employed, in which two triplet TMM biradicals are linked through m-phenylene to produce relatively stable, organic tetraradicals that are characterized by EPR spectroscopy. Under conditions of moderate twisting (4), ferromagnetic coupling is seen, and the tetraradical has a quintet ground state. Severely twisting both TMMs as in 13 disrupts spin communication, and two noninteracting triplets are produced. This is in contrast to other highly twisted m-phenylene derivatives, in which antiferromagnetic coupling has been observed. Surprisingly, severely twisting only one TMM (14) still produces ferromagnetic coupling and a quintet ground state through a spin polarization mechanism analogous to that proposed for 90° twisted ethylene. Several ring-constrained TMMs (17-19) are investigated as models for more nearly planar systems

A multiwavelength study of the remnant of nova GK Persei

We present new observations of the nebular remnant of the old nova GK Persei 1901, in the optical using the 2m HCT and at low radio frequencies using the GMRT. The evolution of the nova remnant indicates shock interaction with the ambient medium, especially in the southwest quadrant. Application of a simple model for the shock and its evolution to determine the time dependence of the radius of the shell in the southwest quadrant indicates that the shell is now expanding into an ambient medium that has a lower density compared to the density of the ambient medium ahead of the shock in 1987.There are indications of a recent interaction of the nova remnant with the ambient medium in the northeast quadrant also. The nova remnant of GK Per is detected at all the observed radio frequencies and is of similar extent as the optical remnant. Putting together our radio observations with VLA archival data on GK Per from 1997, we obtain three interesting results: 1. The spectrum above 1.4 GHz follows a power law with an index -0.7 and below 1.4 GHz follows a power law with an index ~ -0.85. This could be due to the presence of at least two populations of electrons dominating the global emission at different frequencies. 2. We record an annual secular decrease of 2.1% in the flux density of the nova remnant at 1.4 and 4.9 GHz between 1984 and 1997 which has left the spectral index unchanged at -0.7. No such decrease is observed in the flux densities below 1 GHz. 3. We record an increase in the flux density at 0.33 GHz compared to the previous estimate in 1987. We conclude that the remnant of nova GK Per is similar to supernova remnants and in particular, to the young supernova remnant Cas A.Comment: 10 pages; uses A&A style; figures 1, 2 & 6 are in JPEG format. Accepted for publication in Astronomy & Astrophysics. Full paper including Figures 1, 2 & 6 may be downloaded from http://www.iiap.res.in/personnel/gca/gca.htm

The Rise and Fall of Debris Disks: MIPS Observations of h and chi Persei and the Evolution of Mid-IR Emission from Planet Formation

We describe Spitzer/MIPS observations of the double cluster, h and $\chi$ Persei, covering a $\sim$ 0.6 square-degree area surrounding the cores of both clusters. The data are combined with IRAC and 2MASS data to investigate $\sim$ 616 sources from 1.25-24 $\mu m$. We use the long-baseline $K_{s}$-[24] color to identify two populations with IR excess indicative of circumstellar material: Be stars with 24 $\mu m$ excess from optically-thin free free emission and 17 fainter sources (J$\sim$ 14-15) with [24] excess consistent with a circumstellar disk. The frequency of IR excess for the fainter sources increases from 4.5 $\mu m$ through 24 $\mu m$. The IR excess is likely due to debris from the planet formation process. The wavelength-dependent behavior is consistent with an inside-out clearing of circumstellar disks. A comparison of the 24 $\mu m$ excess population in h and $\chi$ Per sources with results for other clusters shows that 24 $\mu m$ emission from debris disks 'rises' from 5 to 10 Myr, peaks at $\sim$ 10-15 Myr, and then 'falls' from $\sim$ 15/20 Myr to 1 Gyr.Comment: 48 pages, 15 figures, accepted for publication in The Astrophysical Journa

An intelligent assistant for exploratory data analysis

In this paper we present an account of the main features of SNOUT, an intelligent assistant for exploratory data analysis (EDA) of social science survey data that incorporates a range of data mining techniques. EDA has much in common with existing data mining techniques: its main objective is to help an investigator reach an understanding of the important relationships ina data set rather than simply develop predictive models for selectd variables. Brief descriptions of a number of novel techniques developed for use in SNOUT are presented. These include heuristic variable level inference and classification, automatic category formation, the use of similarity trees to identify groups of related variables, interactive decision tree construction and model selection using a genetic algorithm

Reduced Caudate and Nucleus Accumbens Response to Rewards in Unmedicated Subjects with Major Depressive Disorder

Objective: Major depressive disorder is characterized by impaired reward processing, possibly due to dysfunction in the basal ganglia. However, few neuroimaging studies of depression have distinguished between anticipatory and consummatory phases of reward processing. Using functional MRI (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that individuals with major depression would show reduced reward-related responses in basal ganglia structures. Method: A monetary incentive delay task was presented to 30 unmedicated individuals with major depressive disorder and 31 healthy comparison subjects during fMRI scanning. Whole-brain analyses focused on neural responses to reward-predicting cues and rewarding outcomes (i.e., monetary gains). Secondary analyses focused on the relationship between anhedonic symptoms and basal ganglia volumes. Results: Relative to comparison subjects, participants with major depression showed significantly weaker responses to gains in the left nucleus accumbens and the caudate bilaterally. Group differences in these regions were specific to rewarding outcomes and did not generalize to neutral or negative outcomes, although relatively reduced responses to monetary penalties in the major depression group emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although participants with major depression showed reduced activation to reward cues in a small sector of the left posterior putamen. In the major depression group, anhedonic symptoms and depression severity were associated with reduced caudate volume bilaterally. Conclusions: These results suggest that basal ganglia dysfunction in major depression may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in major depression is related to caudate volume.Psycholog

Reduced Caudate and Nucleus Accumbens Response to Rewards in Unmedicated Subjects with Major Depressive Disorder

Objective: Major depressive disorder is characterized by impaired reward processing, possibly due to dysfunction in the basal ganglia. However, few neuroimaging studies of depression have distinguished between anticipatory and consummatory phases of reward processing. Using functional MRI (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that individuals with major depression would show reduced reward-related responses in basal ganglia structures. Method: A monetary incentive delay task was presented to 30 unmedicated individuals with major depressive disorder and 31 healthy comparison subjects during fMRI scanning. Whole-brain analyses focused on neural responses to reward-predicting cues and rewarding outcomes (i.e., monetary gains). Secondary analyses focused on the relationship between anhedonic symptoms and basal ganglia volumes. Results: Relative to comparison subjects, participants with major depression showed significantly weaker responses to gains in the left nucleus accumbens and the caudate bilaterally. Group differences in these regions were specific to rewarding outcomes and did not generalize to neutral or negative outcomes, although relatively reduced responses to monetary penalties in the major depression group emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although participants with major depression showed reduced activation to reward cues in a small sector of the left posterior putamen. In the major depression group, anhedonic symptoms and depression severity were associated with reduced caudate volume bilaterally. Conclusions: These results suggest that basal ganglia dysfunction in major depression may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in major depression is related to caudate volume.Psycholog

The Stellar Population of h and chi Persei: Cluster Properties, Membership, and the Intrinsic Colors and Temperatures of Stars

(Abridged) From photometric observations of $\sim$ 47,000 stars and spectroscopy of $\sim$ 11,000 stars, we describe the first extensive study of the stellar population of the famous Double Cluster, h and $\chi$ Persei, down to subsolar masses. Both clusters have E(B-V) $\sim$ 0.52--0.55 and dM = 11.8--11.85; the halo population, while more poorly constrained, likely has identical properties. As determined from the main sequence turnoff, the luminosity of M supergiants, and pre-main sequence isochrones, ages for h Persei, $\chi$ Persei and the halo population all converge on $\approx$ 14 Myr. From these data, we establish the first spectroscopic and photometric membership lists of cluster stars down to early/mid M dwarfs. At minimum, there are $\sim$ 5,000 members within 10' of the cluster centers, while the entire h and $\chi$ Persei region has at least $\sim$ 13,000 and as many as 20,000 members. The Double Cluster contains $\approx$ 8,400 M$_{\odot}$ of stars within 10' of the cluster centers. We estimate a total mass of at least 20,000 M$_{\odot}$. We conclude our study by outlining outstanding questions regarding the properties of h and $\chi$ Persei. From comparing recent work, we compile a list of intrinsic colors and derive a new effective temperature scale for O--M dwarfs, giants, and supergiants.Comment: 88 pages, many figures, Accepted for publication in The Astrophysical Journal Supplements. Contact lead author for version with high-resolution figure