Doctoral Recital

List of performers of performances

Thermodynamic contributions of single internal rA·dA, rC·dC, rG·dG and rU·dT mismatches in RNA/DNA duplexes

The thermodynamic contributions of rA·dA, rC·dC, rG·dG and rU·dT single internal mismatches were measured for 54 RNA/DNA duplexes in a 1 M NaCl buffer using UV absorbance thermal denaturation. Thermodynamic parameters were obtained by fitting absorbance versus temperature profiles using the curve-fitting program Meltwin. The weighted average thermodynamic data were fit using singular value decomposition to determine the eight non-unique nearest-neighbor parameters for each internal mismatch. The new parameters predict the ΔG°37, ΔH° and melting temperature (Tm) of duplexes containing these single mismatches within an average of 0.33 kcal/mol, 4.5 kcal/mol and 1.4°C, respectively. The general trend in decreasing stability for the single internal mismatches is rG·dG > rU·dT > rA·dA > rC·dC. The stability trend for the base pairs 5′ of the single internal mismatch is rG·dC > rC·dG > rA·dT > rU·dA. The stability trend for the base pairs 3′ of the single internal mismatch is rC·dG > rG·dC >> rA·dT > rU·dA. These nearest-neighbor values are now a part of a complete set of single internal mismatch thermodynamic parameters for RNA/DNA duplexes that are incorporated into the nucleic acid assay development software programs Visual oligonucleotide modeling platform (OMP) and ThermoBLAST

Molecular Evolution of Phosphoprotein Phosphatases in Drosophila

Phosphoprotein phosphatases (PPP), these ancient and important regulatory enzymes are present in all eukaryotic organisms. Based on the genome sequences of 12 Drosophila species we traced the evolution of the PPP catalytic subunits and noted a substantial expansion of the gene family. We concluded that the 18–22 PPP genes of Drosophilidae were generated from a core set of 8 indispensable phosphatases that are present in most of the insects. Retropositons followed by tandem gene duplications extended the phosphatase repertoire, and sporadic gene losses contributed to the species specific variations in the PPP complement. During the course of these studies we identified 5, up till now uncharacterized phosphatase retrogenes: PpY+, PpD5+, PpD6+, Pp4+, and Pp6+ which are found only in some ancient Drosophila. We demonstrated that all of these new PPP genes exhibit a distinct male specific expression. In addition to the changes in gene numbers, the intron-exon structure and the chromosomal localization of several PPP genes was also altered during evolution. The G−C content of the coding regions decreased when a gene moved into the heterochromatic region of chromosome Y. Thus the PPP enzymes exemplify the various types of dynamic rearrangements that accompany the molecular evolution of a gene family in Drosophilidae

Gait speed, cognition and falls in people living with mild-to-moderate Alzheimer disease: Data from NILVAD

Background: Previous evidence suggests that slower gait speed is longitudinally associated with cognitive impairment, dementia and falls in older adults. Despite this, the longitudinal relationship between gait speed, cognition and falls in those with a diagnosis of dementia remains poorly explored. We sought to assess this longitudinal relationship in a cohort of older adults with mild to-moderate Alzheimer Disease (AD). Methods: Analysis of data from NILVAD, an 18-month randomised-controlled trial of Nilvadipine in mild to moderate AD. We examined: (i) the cross-sectional (baseline) association between slow gait speed and cognitive function, (ii) the relationship between baseline slow gait speed and cognitive function at 18 months (Alzheimer Disease Assessment Scale, Cognitive Subsection: ADAS-Cog), (iii) the relationship between baseline cognitive function and incident slow gait speed at 18 months and finally (iv) the relationship of baseline slow gait speed and incident falls over the study period. Results: Overall, one-tenth (10.03%, N = 37/369) of participants with mild-to-moderate AD met criteria for slow gait speed at baseline and a further 14.09% (N = 52/369) developed incident slow gait speed at 18 months. At baseline, there was a significant association between poorer cognition and slow gait speed (OR 1.05, 95% CI 1.01-1.09, p = 0.025). Whilst there was no association between baseline slow gait speed and change in ADAS-Cog score at 18 months, a greater cognitive severity at baseline predicted incident slow gait speed over 18 months (OR 1.04, 1.01-1.08, p = 0.011). Further, slow gait speed at baseline was associated with a significant risk of incident falls over the study period, which persisted after covariate adjustment (IRR 3.48, 2.05-5.92, p < 0.001). Conclusions: Poorer baseline cognition was associated with both baseline and incident slow gait speed. Slow gait speed was associated with a significantly increased risk of falls over the study period. Our study adds further evidence to the complex relationship between gait and cognition in this vulnerable group and highlights increased falls risk in older adults with AD and slow gait speed. Trial registration: Secondary analysis of the NILVAD trial (Clincaltrials.gov NCT02017340; EudraCT number 2012-002764-27). First registered: 20/12/2013

The Frequency of Neuropsychological Complaints and Their Relationship to the MMPIA Clinical Scales

The purpose of this study was to obtain base rates in a sample of adolescents with externalizing disorders of the endorsement of symptoms frequently found in patients with neuropsychological dysfunction and, secondly, to determine the personality correlates of these symptoms on the MMPIA. One hundred adolescent psychiatric inpatients with externalizing disorders were administered the Minnesota Multiphasic Personality Inventory Adolescent Version and a checklist of neuropsychological symptoms (such as headache, head injury, seizures, loss of consciousness, etc.). Fifteen of the 24 items on the checklist were endorsed by 20 or more of the subjects. Thirteen of these 15 highly endorsed symptoms, resulted in significant relationships with selected MMPIA Clinical Scales. Univariate ANOVAs calculated between item endorsers and nonendorsers of the fifteen items resulted in significant T-score differences for the 10 MMPIA Clinical Scales (Hs, D, Hy, Pd, Mf, Pa, Pt, Sc, Ma, and Si) and the three validity scales (F, L, and K). Some checklist items (headaches, loss of consciousness, learning problems, and personality changes) resulted in nearly entire profile differences. For the 100 subjects the average order T-scores with the highest elevations on the MMPIA Clinical Scales were: Pd, Ma, Pa, Sc, & D. Highest reported symptom base rates were for headaches (57%), previous hospitalizations (55%), arithmetic disability (49%), use of psychoactive medications (44%), and dizzy spells (37%). The findings of this study suggest that adolescents with externalizing disorders may respond differentially to the MMPIA depending on the presence or absence of symptoms frequently reported in neuropsychological screening interviews

The California Geographer: the first 20 years

From the earliest years of the California Council of Geography\ud Teachers certain founding members intended that the organization should\ud eventually establish its own publications. Lauren Post of San Diego\ud State took the first step in the late 1940's when he began publication\ud of the Newsletter of the CCGT to provide basic communications within\ud the membership. In a few mimeographed pages published several times\ud a year the Newsletter covered annual meeting plans, program developments\ud on the campuses, professional notes and similar matters

Activation of SsoPK4, an Archaeal eIF2α Kinase Homolog, by Oxidized CoA

The eukaryotic protein kinase (ePK) paradigm provides integral components for signal transduction cascades throughout nature. However, while so-called typical ePKs permeate the Eucarya and Bacteria, atypical ePKs dominate the kinomes of the Archaea. Intriguingly, the catalytic domains of the handful of deduced typical ePKs from the archaeon Sulfolobus solfataricus P2 exhibit significant resemblance to the protein kinases that phosphorylate translation initiation factor 2α (eIF2α) in response to cellular stresses. We cloned and expressed one of these archaeal eIF2α protein kinases, SsoPK4. SsoPK4 exhibited protein-serine/threonine kinase activity toward several proteins, including the S. solfataricus homolog of eIF2α, aIF2α. The activity of SsoPK4 was inhibited in vitro by 3ʹ,5ʹ-cyclic AMP (Ki of ~23 µM) and was activated by oxidized Coenzyme A, an indicator of oxidative stress in the Archaea. Activation enhanced the apparent affinity for protein substrates, Km, but had little effect on Vmax. Autophosphorylation activated SsoPK4 and rendered it insensitive to oxidized Coenzyme A

Selectivity of conventional diamond- and novel square-mesh codends in an Australian estuarine penaeid-trawl fishery

The selectivities and relative efficiencies of (i) two conventional diamond-mesh codends with posterior sections 100 and 200 meshes in circumference and (ii) two novel square-mesh codends with different circumferences throughout and comprising panels of square-shaped mesh instead of drawn-strings were investigated in a New South Wales estuarine penaeid-trawl fishery. Paired simultaneous comparisons (using twin trawls) of each of these four treatment codends with their respective small-meshed controls showed that the conventional diamond-mesh codend with a 200 mesh posterior circumference had no detectable selectivity for all sizes of the school prawns, Metapenaeus macleayi and eastern king prawns, Penaeus plebejus encountered. While reducing the posterior circumference to 100 meshes marginally improved selectivity, both of the novel square-mesh codends were the most effective designs in selecting significantly larger prawns across a smaller range of sizes and releasing up to 99% more fish than the conventional diamond-mesh codend with the 200 mesh posterior circumference. The results are discussed in terms of the influences of the geometry of the various codends on their performances and the importance of examining simple changes to codend meshes as a means for augmenting bycatch reduction from penaeid prawn trawls