A common genetic network underlies substance use disorders and disruptive or externalizing disorders

Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors. Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment. These data have been depicted in our studies by extended pedigrees, where ADHD, externalizing symptoms, and SUD segregate and co-segregate. Finally, we applied here a new formal network analysis using the set of significantly replicated genes that have been shown to be either associated and/or linked to ADHD, disruptive behaviors, and SUD in order to detect significantly enriched gene categories for protein and genetic interactions, pathways, co-expression, co-localization, and protein domain similarity. We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented. In summary, we provide compiled evidence of complex networks of genotypes underlying a wide phenotype that involves SUD and externalizing disorders

Kernel-based methods for combining information of several frame surveys

A sample selected from a single sampling frame may not represent adequatly the entire population. Multiple frame surveys are becoming increasingly used and popular among statistical agencies and private organizations, in particular in situations where several sampling frames may provide better coverage or can reduce sampling costs for estimating population quantities of interest. Auxiliary information available at the population level is often categorical in nature, so that incorporating categorical and continuous information can improve the efficiency of the method of estimation. Nonparametric regression methods represent a widely used and flexible estimation approach in the survey context. We propose a kernel regression estimator for dual frame surveys that can handle both continuous and categorical data. This methodology is extended to multiple frame surveys. We derive theoretical properties of the proposed methods and numerical experiments indicate that the proposed estimator perform well in practical settings under different scenarios.Ministerio de Economía y CompetitividadConsejería de Economía, Innovación, Ciencia y Emple

Influence of Ni Catalyst Layer and TiN Diffusion Barrier on Carbon Nanotube Growth Rate

Dense, vertically aligned multiwall carbon nanotubes were synthesized on TiN electrode layers for infrared sensing applications. Microwave plasma-enhanced chemical vapor deposition and Ni catalyst were used for the nanotubes synthesis. The resultant nanotubes were characterized by SEM, AFM, and TEM. Since the length of the nanotubes influences sensor characteristics, we study in details the effects of changing Ni and TiN thickness on the physical properties of the nanotubes. In this paper, we report the observation of a threshold Ni thickness of about 4 nm, when the average CNT growth rate switches from an increasing to a decreasing function of increasing Ni thickness, for a process temperature of 700°C. This behavior is likely related to a transition in the growth mode from a predominantly “base growth” to that of a “tip growth.” For Ni layer greater than 9 nm the growth rate, as well as the CNT diameter, variations become insignificant. We have also observed that a TiN barrier layer appears to favor the growth of thinner CNTs compared to a SiO2 layer

Importance of salt fingering for new nitrogen supply in the oligotrophic ocean.

The input of new nitrogen into the euphotic zone constrains the export of organic carbon to the deep ocean and thereby the biologically mediated long-term CO2 exchange between the ocean and atmosphere. In low-latitude open-ocean regions, turbulence-driven nitrate diffusion from the ocean’s interior and biological fixation of atmospheric N2 are the main sources of new nitrogen for phytoplankton productivity. With measurements across the tropical and subtropical Atlantic, Pacific and Indian oceans, we show that nitrate diffusion (171±190 mmolm 2 d 1) dominates over N2 fixation (9.0±9.4 mmolm 2 d 1) at the time of sampling. Nitrate diffusion mediated by salt fingers is responsible for ca. 20% of the new nitrogen supply in several provinces of the Atlantic and Indian Oceans. Our results indicate that salt finger diffusion should be considered in present and future ocean nitrogen budgets, as it could supply globally 0.23–1.00 TmolNyr 1 to the euphotic zone.MALASPINA (CSD2008-00077)Versión del editor10,015

No evidence for the association of DRD4 with ADHD in a Taiwanese population within-family study

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent and highly heritable childhood disorder. The dopamine D4 receptor (DRD4) gene has shown a genetic association with ADHD in Caucasian populations with meta-analysis indicating a small but significant effect across datasets. It remains uncertain whether this association can be generalised to non-Caucasian ethnic groups. Here we investigate two markers within the DRD4 gene in a Taiwanese population, the exon 3 variable number tandem repeat (VNTR) and a 5' 120 base-pair duplication. METHODS: Within-family transmission disequilibrium tests of association of the 5' 120 base-pair duplication, and exon 3 VNTR in a Taiwanese population. RESULTS: No evidence of association of ADHD with either polymorphism in this population was observed. CONCLUSION: The DRD4 gene markers investigated were not found to be associated with ADHD in this Taiwanese sample. Further work in Taiwanese and other Asian populations will therefore be required to establish whether the reports of association of DRD4 genetic variants in Caucasian samples can be generalised to Asian populations

Candidate high myopia loci on chromosomes 18p and 12q do not play a major role in susceptibility to common myopia

BACKGROUND: To determine whether previously reported loci predisposing to nonsyndromic high myopia show linkage to common myopia in pedigrees from two ethnic groups: Ashkenazi Jewish and Amish. We hypothesized that these high myopia loci might exhibit allelic heterogeneity and be responsible for moderate /mild or common myopia. METHODS: Cycloplegic and manifest refraction were performed on 38 Jewish and 40 Amish families. Individuals with at least -1.00 D in each meridian of both eyes were classified as myopic. Genomic DNA was genotyped with 12 markers on chromosomes 12q21-23 and 18p11.3. Parametric and nonparametric linkage analyses were conducted to determine whether susceptibility alleles at these loci are important in families with less severe, clinical forms of myopia. RESULTS: There was no strong evidence of linkage of common myopia to these candidate regions: all two-point and multipoint heterogeneity LOD scores were < 1.0 and non-parametric linkage p-values were > 0.01. However, one Amish family showed slight evidence of linkage (LOD>1.0) on 12q; another 3 Amish families each gave LOD >1.0 on 18p; and 3 Jewish families each gave LOD >1.0 on 12q. CONCLUSIONS: Significant evidence of linkage (LOD> 3) of myopia was not found on chromosome 18p or 12q loci in these families. These results suggest that these loci do not play a major role in the causation of common myopia in our families studied

Patterns of GPS Tracks Suggest Nocturnal Foraging by Incubating Peruvian Pelicans (Pelecanus thagus)

Most seabirds are diurnal foragers, but some species may also feed at night. In Peruvian pelicans (Pelecanus thagus), the evidence for nocturnal foraging is sparse and anecdotal. We used GPS-dataloggers on five incubating Peruvian pelicans from Isla Lobos de Tierra, Perú, to examine their nocturnality, foraging movements and activities patterns at sea. All instrumented pelicans undertook nocturnal trips during a 5–7 day tracking period. Eighty-seven percent of these trips (n = 13) were strictly nocturnal, whereas the remaining occurred during the day and night. Most birds departed from the island after sunset and returned a few hours after sunrise. Birds traveled south of the island for single-day trips at a maximum range of 82.8 km. Overall, 22% of the tracking period was spent at sea, whereas the remaining time was spent on the island. In the intermediate section of the trip (between inbound and outbound commutes), birds spent 77% of the trip time in floating bouts interspersed by short flying bouts, the former being on average three times longer than the latter. Taken together, the high sinuosity of the bird's tracks during floating bouts, the exclusively nocturnal trips of most individuals, and the fact that all birds returned to the island within a few hours after sunrise suggest that pelicans were actively feeding at night. The nocturnal foraging strategy of Peruvian pelicans may reduce food competition with the sympatric and strictly diurnal Guanay cormorants (Phalacrocorax bougainvillii), Peruvian boobies (Sula variegata) and Blue-footed boobies (S. nebouxii), which were present on the island in large numbers. Likewise, plankton bioluminescence might be used by pelicans as indirect cues to locate anchovies during their upward migration at night. The foraging success of pelicans at night may be enhanced by seizing prey close to the sea surface using a sit-and-wait strategy

Health-related quality of life and mental health in the medium-term aftermath of the Prestige oil spill in Galiza (Spain): a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>In 2002 the oil-tanker <it>Prestige </it>sank off the Galician coast. This study analyzes the effect of this accident on health-related quality of life (HRQoL) and mental health in the affected population.</p> <p>Methods</p> <p>Using random sampling stratified by age and sex, 2700 residents were selected from 7 coastal and 7 inland Galician towns. Two exposure criteria were considered: a) residential exposure, i.e., coast versus interior; and b) individual exposure-unaffected, slightly affected, or seriously affected-according to degree of personal affectation. SF-36, GHQ-28, HADS and GADS questionnaires were used to assess HRQoL and mental health. Association of exposure with suboptimal scores was summarized using adjusted odds ratios (OR) obtained from logistic regression.</p> <p>Results</p> <p>For residential exposure, the SF-36 showed coastal residents as having a lower likelihood of registering suboptimal HRQoL values in physical functioning (OR:0.69; 95%CI:0.54–0.89) and bodily pain (OR:0.74; 95%CI:0.62–0.91), and a higher frequency of suboptimal scores in mental health (OR:1.28; 95%CI:1.02–1.58). None of the dimensions of the other questionnaires displayed statistically significant differences.</p> <p>For individual exposure, no substantial differences were observed, though the SF-36 physical functioning dimension rose (showed better scores) with level of exposure (91.51 unaffected, 93.86 slightly affected, 95.28 seriously affected, p < 0.001).</p> <p>Conclusion</p> <p>Almost one and a half years after the accident, worse HRQoL and mental health levels were not in evidence among subjects exposed to the oil-spill. Nevertheless, some of the scales suggest the possibility of slight impact on the mental health of residents in the affected areas.</p

Role of the IL-1 Pathway in Dopaminergic Neurodegeneration and Decreased Voluntary Movement

Interleukin-1 (IL-1), a proinflammatory cytokine synthesized and released by activated microglia, can cause dopaminergic neurodegeneration leading to Parkinsons disease (PD). However, it is uncertain whether IL-1 can act directly, or by exacerbating the harmful actions of other brain insults. To ascertain the role of the IL-1 pathway on dopaminergic neurodegeneration and motor skills during aging, we compared mice with impaired [caspase-1 knockout (casp1(-/-))] or overactivated IL-1 activity [IL-1 receptor antagonist knockout (IL-1ra(-/-))] to wild-type (wt) mice at young and middle age. Their motor skills were evaluated by the open-field and rotarod tests, and quantification of their dopamine neurons and activated microglia within the substantia nigra were performed by immunohistochemistry. IL-1ra(-/-) mice showed an age-related decline in motor skills, a reduced number of dopamine neurons, and an increase in activated microglia when compared to wt or casp1(-/-) mice. Casp1(-/-) mice had similar changes in motor skills and dopamine neurons, but fewer activated microglia cells than wt mice. Our results suggest that the overactivated IL-1 pathway occurring in IL-1ra(-/-) mice in the absence of inflammatory interventions (e.g., intracerebral injections performed in animal models of PD) increased activated microglia, decreased the number of dopaminergic neurons, and reduced their motor skills. Decreased IL-1 activity in casp1(-/-) mice did not yield clear protective effects when compared with wt mice. In summary, in the absence of overt brain insults, chronic activation of the IL-1 pathway may promote pathological aspects of PD per se, but its impairment does not appear to yield advantages over wt mice.Funding Agencies|John Curtin School of Medical Research, The Australian National University</p