What Aspect of Dependence Does the Fagerström Test for Nicotine Dependence Measure?

Although the Fagerström Test for Nicotine Dependence (FTND) and the Heaviness of Smoking Index (HSI) are widely used, there is a uncertainty regarding what is measured by these scales. We examined associations between these instruments and items assessing different aspects of dependence. Adult current smokers ( , mean age 33.3 years, 61.9% female) completed a web-based survey comprised of items related to demographics and smoking behavior plus (1) the FTND and HSI; (2) the Autonomy over Tobacco Scale (AUTOS) with subscales measuring Withdrawal, Psychological Dependence, and Cue-Induced Cravings; (3) 6 questions tapping smokers’ wanting, craving, or needing experiences in response to withdrawal and the latency to each experience during abstinence; (4) 3 items concerning how smokers prepare to cope with periods of abstinence. In regression analyses the Withdrawal subscale of the AUTOS was the strongest predictor of FTND and HSI scores, followed by taking precautions not to run out of cigarettes or smoking extra to prepare for abstinence. The FTND and its six items, including the HSI, consistently showed the strongest correlations with withdrawal, suggesting that the behaviors described by the items of the FTND are primarily indicative of a difficulty maintaining abstinence because of withdrawal symptoms

Neonatal ureteral obstruction stimulates recruitment of renin-secreting renal cortical cells

Neonatal ureteral obstruction stimulates recruitment of renin-secreting renal cortical cells. Unilateral ureteral obstruction (UUO) in the neonate increases ipsilateral renal renin gene expression, an effect which is mediated by renal nerves. To determine whether neonatal UUO alters the number of renal cortical cells secreting renin and whether this change is modulated by renal nerve activity, newborn Sprague-Dawley rats were subjected to left UUO, right uninephrectomy, or sham operation and studied four weeks thereafter. To evaluate the importance of renal nerves in this response, an additional group of animals underwent chemical sympathectomy with guanethidine. Ureteral obstruction was associated with marked reduction in renal mass in the obstructed kidney and contralateral compensatory hypertrophy, changes which were not altered by sympathectomy. Renin messenger RNA and renal renin content were elevated in the obstructed kidney. The number of cells secreting renin, measured by the reverse hemolytic plaque assay, was markedly increased in the obstructed kidney (45 ± 18 plaques/slide vs. 11 ± 1 plaques/slide in sham animals), but not in the opposite kidney or following uninephrectomy. This effect was not significantly altered by sympathectomy. There was no change in the amount of renin secreted per cell or in the secretory response to Ca++. These results show that UUO results in recruitment of cells not previously secreting renin by a mechanism independent of renal nerve activity. This recruitment occurs without alteration of the quantity of renin secreted per cell or in the normal regulatory effect of Ca++ on renin secretion. An increase in the number of renin-secreting cells may contribute to the activation of the renin-angiotensin system, and thus to the vasoconstriction observed following ureteral obstruction

Aerobic glycolysis is required for spatial memory acquisition but not memory retrieval in mice

The consolidation of newly formed memories and their retrieval are energetically demanding processes. Aerobic glycolysis (AG), also known as the Warburg effect, consists of the production of lactate from glucose in the presence of oxygen. The astrocyte neuron lactate shuttle hypothesis posits that astrocytes process glucose by AG to generate lactate, which is used as a fuel source within neurons to maintain synaptic activity. Studies in mice have demonstrated that lactate transport between astrocytes and neurons is required for long-term memory formation, yet the role of lactate production in memory acquisition and retrieval has not previously been explored. Here, we examined the effect of dichloroacetate (DCA), a chemical inhibitor of lactate production, on spatial learning and memory in mice using the Morris water maze (MWM). In vivo hyperpolarized 13 C-pyruvate magnetic resonance spectroscopy revealed decreased conversion of pyruvate to lactate in the mouse brain following DCA administration, concomitant with a reduction in the phosphorylation of pyruvate dehydrogenase. DCA exposure before each training session in the MWM impaired learning, which subsequently resulted in impaired memory during the probe trial. In contrast, mice that underwent training without DCA exposure, but received a single DCA injection before the probe trial exhibited normal memory. Our findings indicate that AG plays a key role during memory acquisition but is less important for the retrieval of established memories. Thus, the activation of AG may be important for learning-dependent synaptic plasticity rather than the activation of signaling cascades required for memory retrieval

Molecular cloning of KS, a novel rat gene expressed exclusively in the kidney

Molecular cloning of xKSx, a novel rat gene expressed exclusively in the kidney.BackgroundWe aimed to identify genes with kidney specific, developmentally regulated expression. Here we report the cDNA sequence and expression pattern of KS, a novel kidney-specific rat gene.MethodsA partial cDNA was identified by differential display polymerase chain reaction (PCR) of a renal cell fraction enriched for proximal tubular and renin-expressing cells. Using the partial cDNA as a probe, a rat kidney cDNA library was screened. The full-length KS sequence was obtained by PCR amplification of cDNA ends. The expression pattern of KS was investigated by Northern blot. RNA was extracted from several organs of newborn and adult rats, as well as from the kidneys of rats with altered tubular function, that is, rats that had undergone unilateral nephrectomy, unilateral ureteral obstruction, neonatal losartan treatment, and the appropriate control animals. The expression of KS was also investigated in the kidneys of rats with spontaneous or renovascular hypertension.ResultsThe KS cDNA (2426bp) contained one open reading frame encoding a predicted 572 amino acid protein. The derived peptide sequence displayed approximately 70% similarity to the hypertension-related SA gene product and approximately 50% similarity to prokaryotic and eukaryotic acetyl-CoA synthases (EC 6.2.1.1). KS was expressed in the kidney and not in any other organ assayed. KS RNA was not detected in fetal and newborn rat kidney but became apparent after one week of postnatal life. Gene expression was downregulated in rat models of altered tubular function. KS expression was decreased in spontaneously hypertensive rats but not in renovascular hypertension.ConclusionKS, a novel rat gene, exhibits a unique tissue-specific expression exclusively in mature kidneys. The data suggest KS may encode an adenosine monophosphate binding enzyme

Primary Results of a Phase-III, Randomized Controlled Trial of the Behavioral Intervention for Increasing Physical Activity in Multiple Sclerosis Project

Background We undertook a phase-III, randomized controlled trial (RCT) that examined the effectiveness of a behavioral intervention based on social cognitive theory (SCT) and delivered through the Internet using e-learning approaches for immediate and sustained increases in physical activity among persons with multiple sclerosis (MS). Method The study followed a parallel group RCT design. Persons with MS (N = 318) were randomized into either behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions. The conditions were administered over a 6-month period by persons who were uninvolved in screening, recruitment, random assignment, and outcome assessment. There was a 6-month follow-up period without access of conditions. We collected outcome data every 6 months over the 12-month period. The primary outcome was device-measured minutes/day of moderate-to-vigorous physical activity (MVPA). The data analysis involved a modified intent-to-treat approach (i.e. those who received the allocated conditions) using a linear mixed model. Results There was a significant group by time interaction on the primary outcome of device-measured minutes/day of MVPA (p \u3c 0.005). MVPA was increased immediately after the 6-month period in the behavioral intervention compared with control, and this difference was sustained over the 6-month follow-up. Conclusion This study provides evidence for the effectiveness of a widely scalable approach for increasing MVPA in persons with MS

Lactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster

Lactate dehydrogenase (LDH) catalyzes the conversion of glycolysis-derived pyruvate to lactate. Lactate has been shown to play key roles in brain energetics and memory formation. However, lactate levels are elevated in aging and Alzheimer\u27s disease patients, and it is not clear whether lactate plays protective or detrimental roles in these contexts. Here we show that Ldh transcript levels are elevated and cycle with diurnal rhythm in the heads of aged flies and this is associated with increased LDH protein, enzyme activity, and lactate concentrations. To understand the biological significance of increased Ldh gene expression, we genetically manipulated Ldh levels in adult neurons or glia. Overexpression of Ldh in both cell types caused a significant reduction in lifespan whereas Ldh down-regulation resulted in lifespan extension. Moreover, pan-neuronal overexpression of Ldh disrupted circadian locomotor activity rhythms and significantly increased brain neurodegeneration. In contrast, reduction of Ldh in neurons delayed age-dependent neurodegeneration. Thus, our unbiased genetic approach identified Ldh and lactate as potential modulators of aging and longevity in flies

Semiconductor Surface Studies

Contains an introduction, reports on two research projects and a list of publications.Joint Services Electronics Program Contract DAAL03-92-C-000

Acute Liver Failure (ALF) in Pregnancy: How Much Is Pregnancy Related?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163471/1/hep31144.pd

Ameliorating Systematic Uncertainties in the Angular Clustering of Galaxies: A Study using SDSS-III

We investigate the effects of potential sources of systematic error on the angular and photometric redshift, z_phot, distributions of a sample of redshift 0.4 < z < 0.7 massive galaxies whose selection matches that of the Baryon Oscillation Spectroscopic Survey (BOSS) constant mass sample. Utilizing over 112,778 BOSS spectra as a training sample, we produce a photometric redshift catalog for the galaxies in the SDSS DR8 imaging area that, after masking, covers nearly one quarter of the sky (9,913 square degrees). We investigate fluctuations in the number density of objects in this sample as a function of Galactic extinction, seeing, stellar density, sky background, airmass, photometric offset, and North/South Galactic hemisphere. We find that the presence of stars of comparable magnitudes to our galaxies (which are not traditionally masked) effectively remove area. Failing to correct for such stars can produce systematic errors on the measured angular auto-correlation function, w, that are larger than its statistical uncertainty. We describe how one can effectively mask for the presence of the stars, without removing any galaxies from the sample, and minimize the systematic error. Additionally, we apply two separate methods that can be used to correct the systematic errors imparted by any parameter that can be turned into a map on the sky. We find that failing to properly account for varying sky background introduces a systematic error on w. We measure w, in four z_phot slices of width 0.05 between 0.45 < z_phot < 0.65 and find that the measurements, after correcting for the systematic effects of stars and sky background, are generally consistent with a generic LambdaCDM model, at scales up to 60 degrees. At scales greater than 3 degrees and z_phot > 0.5, the magnitude of the corrections we apply are greater than the statistical uncertainty in w.Comment: Accepted by MNRA

Semiconductor Surface Studies

Contains an introduction, reports on two research projects and a list of publications.Joint Services Electronics Program Contract DAALO3-92-C-000