Neurogenetic interactions and aberrant behavioral co-morbidity of attention deficit hyperactivity disorder (ADHD): dispelling myths

Background

Attention Deficit Hyperactivity Disorder, commonly referred to as ADHD, is a common, complex, predominately genetic but highly treatable disorder, which in its more severe form has such a profound effect on brain function that every aspect of the life of an affected individual may be permanently compromised. Despite the broad base of scientific investigation over the past 50 years supporting this statement, there are still many misconceptions about ADHD. These include believing the disorder does not exist, that all children have symptoms of ADHD, that if it does exist it is grossly over-diagnosed and over-treated, and that the treatment is dangerous and leads to a propensity to drug addiction. Since most misconceptions contain elements of truth, where does the reality lie?

Results

We have reviewed the literature to evaluate some of the claims and counter-claims. The evidence suggests that ADHD is primarily a polygenic disorder involving at least 50 genes, including those encoding enzymes of neurotransmitter metabolism, neurotransmitter transporters and receptors. Because of its polygenic nature, ADHD is often accompanied by other behavioral abnormalities. It is present in adults as well as children, but in itself it does not necessarily impair function in adult life; associated disorders, however, may do so. A range of treatment options is reviewed and the mechanisms responsible for the efficacy of standard drug treatments are considered.

Conclusion

The genes so far implicated in ADHD account for only part of the total picture. Identification of the remaining genes and characterization of their interactions is likely to establish ADHD firmly as a biological disorder and to lead to better methods of diagnosis and treatment.

     

Molecular docking of potential inhibitors with the mTOR protein

The mTOR (mammalian or mechanistic Target of Rapamycin) is linked with oral cancer. Therefore, it is of interest to study the molecular docking-based binding of paclitaxel (a FDA approved drug for oral cancer) and its analogues with mTOR. Hence, we report the binding features of 10-Deacetyltaxol, 7-Epi-10-deacetyltaxol, 7-Epi-Taxol and 6alpha-Hydroxypaclitaxel with mTOR for further consideration.     

Ecosystem changes associated with grazing in subhumid South American grasslands

Question: What are the changes in vegetation structure, soil attributes and mesofauna associated with grazing in mesic grasslands? Location: Southern Campos of the Río de la Plata grasslands, in south‐central Uruguay. Methods: We surveyed seven continuously grazed and ungrazed paired plots. Plant and litter cover were recorded on three 5‐m interception lines placed parallel to the fence in each plot. We extracted soil fauna from a 10 cm deep composite sample and analysed the oribatids. Soil attributes included bulk density, water content, organic carbon (in particulate and mineral associated organic matter) and nitrogen content and root biomass at different depths. Changes in floristic, Plant Functional Types and mesofauna composition were analysed by Non‐metric Multidimensional Scaling. Results: Species number was lower in ungrazed than in grazed plots. Of 105 species in grazed plots only three were exotics. Shrub and litter cover were significantly higher inside the exclosures, while the cover of Cyperaceae‐Juncaceae was lower. Grazing treatments differed significantly in plant and oribatid species composition. Grazing exclusion significantly reduced soil bulk density and increased soil water content. Carbon content in particulate organic matter was lower in the upper soil of ungrazed sites, but deeper in the profile, grazing exclosures had 8% more carbon in the mineral associated organic matter. Conclusions Our results generally agree with previous studies but deviate from the results of previous analyses in (1) the increase of shrub cover in ungrazed sites; (2) the redistribution of the soil organic carbon in the profile and (3) the low invasibility of the prairies regardless of grazing regime.     

Role of exotic tree stands on the current distribution and social behaviour of Swainson's hawk, Buteo swainsoni in the Argentine Pampas

Aim The Argentine Pampas was extensively and abruptly altered by European colonization. Between 1880 and 1885 the indigenous human inhabitants were completely displaced, and native grasslands were replaced by exotic pasture plants and crops. One of the most important ecological changes in the Pampas landscape, the introduction of tall exotic tree species, has received little attention, and its effect on wildlife has never been assessed. We have made an intensive survey of habitat use of Swainson's hawk, Buteo swainsoni in its most important non‐breeding quarters, the Pampas of Argentina, aiming to characterize the sites used by hawks for communal roosting. Location Pampas grasslands, Argentina. Methods We surveyed 30,000 km of roads by car during the austral summer from 2001 to 2004, covering the main non‐breeding area occupied by Swainson's hawks. Their roost sites were located by direct observation of birds roosting in tree stands close to the roads, by surveying potential roost sites around places where groups of pre‐ and post‐roosting hawks were recorded, and by gathering information from local farmers. Results Swainson's hawks exclusively used stands of exotic tree species for roosting. Eucalyptus viminalis was present in all 34 roosts surveyed, and in 59% of them it was the only species present. The remaining exotic tree species were the Siberian elm, Ulmus pumila, pines (Pinus spp.) and cypress (Cupressus spp.). Flock sizes at roost sites were unusually high for a raptor, with an average of 658 individuals (range 8–5000 hawks, n = 27 flocks). Main conclusions The introduction of exotic trees may have resulted in the expansion of the suitable habitat for Swainson's hawks, permitting a recent colonization of the Argentine Pampas. Tree stands may have also changed the communal roosting behaviour of this raptor, by virtue of their providing new structural elements in a region that almost completely lacked trees prior to European occupation.     

The cytoplasmic domain of MT1-MMP is dispensable for migration augmentation but necessary to mediate viability of MCF-7 breast cancer cells

Membrane-type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease that regulates ECM degradation, proMMP-2 activation, and varied cellular processes including migration and viability. MT1-MMP is believed to be a central mediator of tumourigenesis whose role is dictated by its functionally distinct protein domains. Both the localization and signal transduction capabilities of MT1-MMP are dependent on its cytoplasmic domain, exemplifying diverse regulatory functions. To further our understanding of the multifunctional contributions of MT1-MMP to cellular processes, we overexpressed cytoplasmic domain altered constructs in MCF-7 breast cancer cells and analyzed migration and viability in 2D culture conditions, morphology in 3D Matrigel culture, and tumorigenic ability in vivo. We found that the cytoplasmic domain was not needed for MT1-MMP mediated migration promotion, but was necessary to maintain viability during serum depravation in 2D culture. Similarly, during 3D Matrigel culture the cytoplasmic domain of MT1-MMP was not needed to initiate a protrusive phenotype, but was necessary to prevent colony blebbing when cells were serum deprived. We also tested in vivo tumorigenic potential to show that cells expressing cytoplasmic domain altered constructs demonstrated a reduced ability to vascularize tumours. These results suggest that the cytoplasmic domain regulates MT1-MMP function in a manner required for cell survival, but is dispensable for cell migration.     

Population genetics of the endangered Crowned Solitary Eagle (<Emphasis Type="Italic">Buteogallus coronatus</Emphasis>) in South America

The Crowned Solitary Eagle (Buteogallus coronatus) is one of the rarest and most severely threatened birds of prey in the Neotropical region. We studied levels of neutral genetic diversity, population structure, and the demographic history of the species using 55 contemporary samples covering a large fraction of the species range, which were genotyped at 17 microsatellite loci. Our results indicated genetic homogeneity across the sampled regions, which may be explained by a high dispersal capability of Crowned Solitary Eagles resulting in high gene flow or relatively recent population expansion. Further demographic tests revealed that the species has experienced a recent demographic reduction, but inbreeding was not detected. The existing connectivity between geographically separated populations may have buffered the negative effects of the demographic bottleneck. Alternatively, the demographic reduction may be too recent to detect a genetic signature due to the long generation time of the species. Potential conservation strategies, including the possibility of translocations of individuals, are discussed.     

Repeated triggering of sporulation in Bacillus subtilis selects against a protein that affects the timing of cell division

Bacillus subtilis sporulation is a last-resort phenotypical adaptation in response to starvation. The regulatory network underlying this developmental pathway has been studied extensively. However, how sporulation initiation is concerted in relation to the environmental nutrient availability is poorly understood. In a fed-batch fermentation set-up, in which sporulation of ultraviolet (UV)-mutagenized B. subtilis is repeatedly triggered by periods of starvation, fitter strains with mutated tagE evolved. These mutants display altered timing of phenotypical differentiation. The substrate for the wall teichoic acid (WTA)-modifying enzyme TagE, UDP-glucose, has recently been shown to be an intracellular proxy for nutrient availability, and influences the timing of cell division. Here we suggest that UDP-glucose also influences timing of cellular differentiation.     

Chipping away at major depressive disorder

An intriguing recent study examines the role of miR-1202, a glutamate receptor regulating microRNA, in regulating major depressive disorder.