Triton-stimulated nucleoside diphosphatase activity: Subcellular localization in corn root homogenates

Summary The distribution of latent UDPase activity (cold storage-activated) is similar to Triton-stimulated UDPase activity in membrane fractions separated by differential centrifugation as well as fractions purified by linear sucrose density centrifugation. The Triton-stimulated UDPase activity appears to be a specific marker for Golgi membranes in corn root homogenates. Detergent-activated UDPase activity provides a more reliable, less cumbersome way to monitor Golgi membranes compared to cold storage-activation and this marker can be used on fresh preparations.This research was supported in part by NSF grant CDP-7927121 and funds received from the Bronfman Science Center, Williams College.     

An Evolutionary Comparison of the Handicap Principle and Hybrid Equilibrium Theories of Signaling

The handicap principle has come under significant challenge both from empirical studies and from theoretical work. As a result, a number of alternative explanations for honest signaling have been proposed. This paper compares the evolutionary plausibility of one such alternative, the “hybrid equilibrium,” to the handicap principle. We utilize computer simulations to compare these two theories as they are instantiated in Maynard Smith’s Sir Philip Sidney game. We conclude that, when both types of communication are possible, evolution is unlikely to lead to handicap signaling and is far more likely to result in the partially honest signaling predicted by hybrid equilibrium theory.     

Establishing genomic tools and resources for Guizotia abyssinica (L.f.) Cass.-the development of a library of expressed sequence tags, microsatellite loci, and the sequencing of its chloroplast genome

We present an EST library, chloroplast genome sequence, and nuclear microsatellite markers that were developed for the semi-domesticated oilseed crop noug (Guizotia abyssinica) from Ethiopia. The EST library consists of 25 711 Sanger reads, assembled into 17 538 contigs and singletons, of which 4781 were functionally annotated using the Arabidopsis Information Resource (TAIR). The age distribution of duplicated genes in the EST library shows evidence of two paleopolyploidizations—a pattern that noug shares with several other species in the Heliantheae tribe (Compositae family). From the EST library, we selected 43 microsatellites and then designed and tested primers for their amplification. The number of microsatellite alleles varied between 2 and 10 (average 4.67), and the average observed and expected heterozygosities were 0.49 and 0.54, respectively. The chloroplast genome was sequenced de novo using Illumina’s sequencing technology and completed with traditional Sanger sequencing. No large re-arrangements were found between the noug and sunflower chloroplast genomes, but 1.4% of sites have indels and 1.8% show sequence divergence between the two species. We identified 34 tRNAs, 4 rRNA sequences, and 80 coding sequences, including one region (trnH-psbA) with 15% sequence divergence between noug and sunflower that may be particularly useful for phylogeographic studies in noug and its wild relatives.     

Rampant gene exchange across a strong reproductive barrier between the annual sunflowers, Helianthus annuus and H. petiolaris

Plant species may remain morphologically distinct despite gene exchange with congeners, yet little is known about the genomewide pattern of introgression among species. Here we analyze the effects of persistent gene flow on genomic differentiation between the sympatric sunflower species Helianthus annuus and H. petiolaris. While the species are strongly isolated in testcrosses, genetic distances at 108 microsatellite loci and 14 sequenced genes are highly variable and much lower (on average) than for more closely related but historically allopatric congeners. Our analyses failed to detect a positive association between levels of genetic differentiation and chromosomal rearrangements (as reported in a prior publication) or proximity to QTL for morphological differences or hybrid sterility. However, a significant increase in differentiation was observed for markers within 5 cM of chromosomal breakpoints. Together, these results suggest that islands of differentiation between these two species are small, except in areas of low recombination. Furthermore, only microsatellites associated with ESTs were identified as outlier loci in tests for selection, which might indicate that the ESTs themselves are the targets of selection rather than linked genes (or that coding regions are not randomly distributed). In general, these results indicate that even strong and genetically complex reproductive barriers cannot prevent widespread introgression.     

Analysis of TBX1 variation in patients with psychotic and affective disorders

A significant portion of patients with 22q11 deletion syndrome (22q11DS) develop psychiatric disorders, including schizophrenia and other psychotic and affective symptoms, and the responsible gene/s are assumed to also play a significant role in the etiology of nonsyndromic psychiatric disease. The most common psychiatric diagnosis among patients with 22q11DS is schizophrenia, thought to result from neurotransmitter imbalances and also from disturbed brain development. Several genes in the 22q11 region with known or suspected roles in neurotransmitter metabolism have been analyzed in patients with isolated schizophrenia; however, their contribution to the disease remains controversial. Haploinsufficiency of the TBX1 gene has been shown to be sufficient to cause the core physical malformations associated with 22q11DS in mice and humans and via abnormal brain development could contribute to 22q11DS-related and isolated psychiatric disease. 22q11DS populations also have increased rates of psychiatric conditions other than schizophrenia, including mood disorders. We therefore analyzed variations at the TBX1 locus in a cohort of 446 white patients with psychiatric disorders relevant to 22q11DS and 436 ethnically matched controls. The main diagnoses included schizophrenia (n = 226), schizoaffective disorder (n = 67), bipolar disorder (n = 82), and major depressive disorder (n = 29). We genotyped nine tag SNPs in this sample but did not observe significant differences in allele or haplotype frequencies in any of the analyzed groups (all affected, schizophrenia and schizoaffective disorder, schizophrenia alone, and bipolar disorder and major depressive disorder) compared with the control group. Based on these results we conclude that TBX1 variation does not make a strong contribution to the genetic etiology of nonsyndromic forms of psychiatric disorders commonly seen in patients with 22q11DS.     

MK-8825: a potent and selective CGRP receptor antagonist with good oral activity in rats

Rational modification of the clinically tested CGRP receptor antagonist MK-3207 (3) afforded an analogue with increased unbound fraction in rat plasma and enhanced aqueous solubility, 2-[(8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(6S)-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl]acetamide (MK-8825) (6). Compound 6 maintained similar affinity to 3 at the human and rat CGRP receptors but possessed significantly improved in vivo potency in a rat pharmacodynamic model. The overall profile of 6 indicates it should find utility as a rat tool to investigate effects of CGRP receptor blockade in vivo.     

Activities of Daily Living,Depression, and Quality of Life in Parkinson's Disease

This study examined whether activities of daily living (ADL) mediate the relationship between depression and health-related quality of life (HR-QOL) in people with Parkinson''s disease (PD). A cross-sectional, correlational research design examined data from 174 participants who completed the Geriatric Depression Scale (GDS-15), Parkinson''s Disease Questionnaire-39 (PDQ-39), and Unified Parkinson''s Disease Rating Scale-section 2 (UPDRS-section 2 [ADL]). Multiple Regression Analysis (MRA) was used to examine the mediator model. Depression and ADL significantly (p<.001) predicted HR-QOL, and depression significantly (p<.001) predicted ADL. Whilst ADL did not impact on the relationship between depression and HR-QOL, there was a significant (p<.001) indirect effect of depression on HR-QOL via ADL, suggesting both direct and indirect (via ADL) effects of depression on HR-QOL. The magnitude of this effect was moderate (R² = .13). People with PD who report depression also experience greater difficulty completing ADL, which impacts upon their HR-QOL. It is recommended that clinicians adopt a multidisciplinary approach to care by combining pharmacological treatments with psycho/occupational therapy, thereby alleviating the heterogeneous impact of motor and non-motor symptoms on HR-QOL in people with PD.     

A new method for the study of velopharyngeal function using gated magnetic resonance imaging

The purpose of this project was to assess the feasibility of imaging the velopharynx of adult volunteers during repetitive speech, using gated magnetic resonance imaging (MRI). Although a number of investigators have used conventional MRI in the study of the human vocal tract, the mismatch between the lengthy time necessary to acquire sufficiently detailed images and the rapidity of movement of the vocal tract during speech has forced investigators to acquire images either while the subject is at rest or during sustained utterances. The technique used here acquired a portion of each image during repetitive utterances, building the full image over multiple utterance cycles. The velopharyngeal portal was imaged on a 1.5-Tesla GE Signa LX 8.2 platform with gated fast spoiled gradient echo protocol. An external 1-Hertz trigger was fed to the cardiac gate. Subjects synchronized utterance of consonant-vowel syllables to a flashing light synchronized with the external trigger. Each acquisition of 30 phases per second at a single-slice location took 22 to 29 seconds. Four consonant-vowel syllables (/pa/, /ma/, /sa/, and /ka/) were evaluated. Subjects vocalized throughout the acquisition, beginning 5 to 6 seconds beforehand to establish a regular rhythm. Imaging of the velopharyngeal portal was performed for sagittal, velopharyngeal axial (aligned perpendicular to the "knee" of the velum), axial, and coronal planes. Volumes were obtained by sequential acquisition of six to 10 slices (each with 30 phases) in the axial or sagittal planes during repetition of the /pa/ syllable. Spatiotemporal volumes of the single-slice data were sectioned to provide time-motion images (analogous to M-mode echocardiograms). Three-dimensional dynamic volume renderings of palate motion were displayed interactively (Vortex; CieMed, Singapore). A method suitable for the collection and visualization of four-dimensional information regarding monosyllabic speech using gated MRI was developed. These techniques were applied to a population of adult volunteer subjects with no history of speech problems and two patients with a history of cleft lip and palate. The techniques allowed good real-time visualization of velopharyngeal anatomy during its entire range of motion and was also able to image pathology-specific anatomic differences in the subjects with cleft lip and cleft palate. These methods may be applicable to a wide spectrum of problems in speech physiology research and for clinical decision-making regarding surgery for speech and outcomes analysis.     

Phylogeography of the pantropical sea urchin Tripneustes: contrasting patterns of population structure between oceans

To understand how allopatric speciation proceeds, we need information on barriers to gene flow, their antiquity, and their efficacy. For marine organisms with planktonic larvae, much of this information can only be obtained through the determination of divergence between populations. We evaluated the importance of ocean barriers by studying the mitochondrial DNA phylogeography of Tripneustes, a pantropical genus of shallow water sea urchin. A region of cytochrome oxidase I (COI) was sequenced in 187 individuals from locations around the globe. The COI phylogeny agreed with a previously published phylogeny of bindin that barriers important to the evolution of Tripneustes are: (1) the cold water upwelling close to the tip of South Africa, (2) the Isthmus of Panama, (3) the long stretch of deep water separating the eastern from the western Atlantic, and (4) the freshwater plume of the Orinoco and the Amazon rivers between the Caribbean and the coast of Brazil. These barriers have previously been shown to be important in at least a subset of the shallow water marine organisms in which phylogeography has been studied. In contrast, the Eastern Pacific Barrier, 5000 km of deep water between the central and the eastern Pacific that has caused the deepest splits in other genera of sea urchins, is remarkably unimportant as a cause of genetic subdivision in Tripneustes. There is also no discernible subdivision between the Pacific and Indian Ocean populations of this genus. The most common COI haplotype is found in the eastern, central, and western Pacific as well as the Indian Ocean. Morphology, COI, and bindin data agree that T. depressus from the eastern Pacific and T. gratilla from the western Pacific are, in fact, the same species. The distribution of haplotype differences in the Indo-Pacific exhibits characteristics expected from a sea urchin genus with ephemeral local populations, but with high fecundity, dispersal, and growth: there is little phylogenetic structure, and mismatch distributions conform to models of recent population expansion on a nearly global scale. Yet, comparisons between local populations produce large and significant F(ST) values, indicating nonrandom haplotype distribution. This apparent local differentiation is only weakly reflected in regional divergence, and there is no evidence of isolation by distance in correlations between F(ST) values and either geographical or current distance. Thus, Tripneustes in the Indo-Pacific (but not in the Atlantic) seems to be one large metapopulation spanning two oceans and containing chaotic, nonequilibrium local variation, produced by the haphazard arrival of larvae or by unpredictable local extinction.